PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
19238353-4	2009	Such studies can be a valuable complementary approach to more commonly used pharmacological analyses using agents such as ruboxistaurin mesylate (Arxxant, LY333531), which is claimed to specifically inhibit the PKC-beta-isoform.	ruboxistaurin	155-163	protein kinase C, beta	Mus musculus	211-219
20875828-3	2010	Owing to the key role of PKC-beta in AGEs-induced vascular dysfunction, we investigated effects of blocking PKC-beta by LY333531 on macrophage adhesion to HUVEC and the related mechanism.	ruboxistaurin	120-128	protein kinase C beta	Homo sapiens	108-116
20197783-3	2010	In this study, we used isolated rat brain capillaries to show that the TNF-alpha-induced reduction of P-glycoprotein activity was prevented by a PKCbeta(I/II) inhibitor, LY333531, and mimicked by a PKCbeta(I/II) activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA).	ruboxistaurin	170-178	tumor necrosis factor	Rattus norvegicus	71-80
20197783-3	2010	In this study, we used isolated rat brain capillaries to show that the TNF-alpha-induced reduction of P-glycoprotein activity was prevented by a PKCbeta(I/II) inhibitor, LY333531, and mimicked by a PKCbeta(I/II) activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA).	ruboxistaurin	170-178	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	102-116
20197783-3	2010	In this study, we used isolated rat brain capillaries to show that the TNF-alpha-induced reduction of P-glycoprotein activity was prevented by a PKCbeta(I/II) inhibitor, LY333531, and mimicked by a PKCbeta(I/II) activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA).	ruboxistaurin	170-178	protein kinase C, beta	Rattus norvegicus	145-152
20197783-3	2010	In this study, we used isolated rat brain capillaries to show that the TNF-alpha-induced reduction of P-glycoprotein activity was prevented by a PKCbeta(I/II) inhibitor, LY333531, and mimicked by a PKCbeta(I/II) activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA).	ruboxistaurin	170-178	protein kinase C, beta	Rattus norvegicus	198-205
20079359-1	2010	The PKC-beta inhibitor ruboxistaurin (RBX or LY333531) prevents diabetic renal and retinal microvascular complications.	ruboxistaurin	23-36	protein kinase C, beta	Rattus norvegicus	4-12
20079359-1	2010	The PKC-beta inhibitor ruboxistaurin (RBX or LY333531) prevents diabetic renal and retinal microvascular complications.	ruboxistaurin	45-53	protein kinase C, beta	Rattus norvegicus	4-12
20044781-1	2010	PKC-beta inhibitor Ruboxistaurin (RBX or LY333531) can be used to reverse diabetic microvascular complication.	ruboxistaurin	19-32	protein kinase C, beta	Rattus norvegicus	0-8
20044781-1	2010	PKC-beta inhibitor Ruboxistaurin (RBX or LY333531) can be used to reverse diabetic microvascular complication.	ruboxistaurin	41-49	protein kinase C, beta	Rattus norvegicus	0-8
19825373-0	2010	Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.	ruboxistaurin	0-13	protein kinase C, beta	Mus musculus	17-24
19825373-0	2010	Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.	ruboxistaurin	0-13	mitogen-activated protein kinase 3	Mus musculus	110-116
19825373-0	2010	Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.	ruboxistaurin	0-13	thymoma viral proto-oncogene 1	Mus musculus	121-124
19825373-1	2010	Ruboxistaurin, a protein kinase C (PKC) beta inhibitor, exhibits significant anti-angiogenic activity that reduces the response of vascular endothelial cells to stimulation by vascular endothelial growth factor (VEGF).	ruboxistaurin	0-13	protein kinase C, beta	Mus musculus	17-44
19825373-1	2010	Ruboxistaurin, a protein kinase C (PKC) beta inhibitor, exhibits significant anti-angiogenic activity that reduces the response of vascular endothelial cells to stimulation by vascular endothelial growth factor (VEGF).	ruboxistaurin	0-13	vascular endothelial growth factor A	Mus musculus	176-210
19825373-1	2010	Ruboxistaurin, a protein kinase C (PKC) beta inhibitor, exhibits significant anti-angiogenic activity that reduces the response of vascular endothelial cells to stimulation by vascular endothelial growth factor (VEGF).	ruboxistaurin	0-13	vascular endothelial growth factor A	Mus musculus	212-216
19825373-5	2010	Ruboxistaurin inhibited formation, proliferation, and migration of VEGF-induced human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner.	ruboxistaurin	0-13	vascular endothelial growth factor A	Homo sapiens	67-71
19825373-9	2010	These findings indicate that ruboxistaurin has anti-angiogenic effects both in vitro and in vivo that are exerted partly via suppressing the phosphorylation of ERK1/2 and Akt.	ruboxistaurin	29-42	mitogen-activated protein kinase 3	Mus musculus	160-166
19825373-9	2010	These findings indicate that ruboxistaurin has anti-angiogenic effects both in vitro and in vivo that are exerted partly via suppressing the phosphorylation of ERK1/2 and Akt.	ruboxistaurin	29-42	thymoma viral proto-oncogene 1	Mus musculus	171-174
19929710-0	2009	Ruboxistaurin: PKC-beta inhibition for complications of diabetes.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	15-23
19929710-3	2009	An inhibitor of the PKC-beta isoform ruboxistaurin (RBX) has in vitro and in vivo benefits in ameliorating disturbances of cell regulation and blood flow related to hyperglycemia.	ruboxistaurin	37-50	protein kinase C beta	Homo sapiens	20-28
19929710-3	2009	An inhibitor of the PKC-beta isoform ruboxistaurin (RBX) has in vitro and in vivo benefits in ameliorating disturbances of cell regulation and blood flow related to hyperglycemia.	ruboxistaurin	52-55	protein kinase C beta	Homo sapiens	20-28
20840471-8	2011	The effects of ROCK inhibitors in diabetic rats were modulated by prior protein kinase C (PKC)beta inhibition with ruboxistaurin, which abolished their effects on FF.	ruboxistaurin	115-128	protein kinase C, beta	Rattus norvegicus	90-98
19587355-5	2009	RESULTS: Exposure of cardiomyocytes to high glucose activated PKCbeta(2) and increased iNOS expression that was prevented by LY333531.	ruboxistaurin	125-133	protein kinase C, beta	Rattus norvegicus	62-69
19587355-5	2009	RESULTS: Exposure of cardiomyocytes to high glucose activated PKCbeta(2) and increased iNOS expression that was prevented by LY333531.	ruboxistaurin	125-133	nitric oxide synthase 2	Rattus norvegicus	87-91
19587355-6	2009	Similarly, treatment of VSMC with LY333531 prevented high glucose-induced activation of nuclear factor kappaB, extracellular signal-related kinase, and iNOS overexpression.	ruboxistaurin	34-42	nitric oxide synthase 2	Rattus norvegicus	58-156
19587355-8	2009	Administration of LY333531 (1 mg/kg/day) decreased iNOS expression and formation of peroxynitrite in the heart and superior mesenteric arteries and corrected the cardiovascular abnormalities in STZ-induced diabetic rats, an action that was also observed with a selective iNOS inhibitor, L-NIL.	ruboxistaurin	18-26	nitric oxide synthase 2	Rattus norvegicus	51-55
19587355-8	2009	Administration of LY333531 (1 mg/kg/day) decreased iNOS expression and formation of peroxynitrite in the heart and superior mesenteric arteries and corrected the cardiovascular abnormalities in STZ-induced diabetic rats, an action that was also observed with a selective iNOS inhibitor, L-NIL.	ruboxistaurin	18-26	nitric oxide synthase 2	Rattus norvegicus	271-275
19556521-0	2009	Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach.	ruboxistaurin	133-146	protein kinase C, alpha	Mus musculus	0-22
19556521-7	2009	Infusion of ruboxistaurin (LY333531), an orally available PKCalpha/beta/gamma inhibitor, increased cardiac contractility in wild-type and PKCbetagamma(-/-) mice, but not in PKCalpha(-/-) mice.	ruboxistaurin	12-25	protein kinase C alpha	Homo sapiens	58-66
19556521-7	2009	Infusion of ruboxistaurin (LY333531), an orally available PKCalpha/beta/gamma inhibitor, increased cardiac contractility in wild-type and PKCbetagamma(-/-) mice, but not in PKCalpha(-/-) mice.	ruboxistaurin	27-35	protein kinase C alpha	Homo sapiens	58-66
19556521-9	2009	Ruboxistaurin was also administered to PKCbetagamma(-/-) mice subjected to pressure overload, resulting in less death and heart failure, implicating PKCalpha as the primary target of this drug in mitigating heart disease.	ruboxistaurin	0-13	protein kinase C, alpha	Mus musculus	149-157
19482966-6	2009	The selective inhibition of endothelial PKC-beta with ruboxistaurin (1 microM) abolished the adipose-induced impairment of bradykinin-mediated coronary vasodilation and the endothelial production of nitric oxide.	ruboxistaurin	54-67	kininogen 1	Canis lupus familiaris	123-133
19036858-5	2009	Significant reduction in atherosclerosis of approximately 2-fold was observed in apoE(-/-) mice fed ruboxistaurin chow (PKCbeta inhibitor) vs. vehicle.	ruboxistaurin	100-113	apolipoprotein E	Mus musculus	81-85
19036858-5	2009	Significant reduction in atherosclerosis of approximately 2-fold was observed in apoE(-/-) mice fed ruboxistaurin chow (PKCbeta inhibitor) vs. vehicle.	ruboxistaurin	100-113	protein kinase C, beta	Mus musculus	120-127
19808328-5	2009	Diabetic rats were randomized to receive either vehicle or the PKC-beta inhibitor, ruboxistaurin (20 mg/kg per d) and followed for 6 weeks.	ruboxistaurin	83-96	protein kinase C, beta	Rattus norvegicus	63-71
19808328-7	2009	Collagen I deposition and cardiomyocyte hypertrophy were both reduced in diabetic animals treated with ruboxistaurin (P<0.01), as was phosphorylated-Smad2, an index of transforming growth factor-beta activity (P<0.01 for all, versus untreated diabetic rats).	ruboxistaurin	103-116	SMAD family member 2	Rattus norvegicus	152-157
18989348-1	2009	PURPOSE: In PKC-DRS2, the efficacy of the oral PKC-beta inhibitor, ruboxistaurin 32 mg/day, was measured by the primary end point of sustained moderate visual loss (SMVL: a > or = 15 letter decrease from baseline on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart sustained at least for the last 6 months of study participation).	ruboxistaurin	67-80	protein kinase C beta	Homo sapiens	47-55
19211711-8	2009	In vivo, the PKC-beta inhibitor ruboxistaurin prevented Akt activation in the renal cortex of diabetic rats.	ruboxistaurin	32-45	protein kinase C, beta	Rattus norvegicus	13-21
19211711-8	2009	In vivo, the PKC-beta inhibitor ruboxistaurin prevented Akt activation in the renal cortex of diabetic rats.	ruboxistaurin	32-45	AKT serine/threonine kinase 1	Rattus norvegicus	56-59
18949545-0	2009	Selective PKC beta inhibition with ruboxistaurin and endothelial function in type-2 diabetes mellitus.	ruboxistaurin	35-48	protein kinase C beta	Homo sapiens	10-18
18949545-5	2009	METHODS: The goal of this double-masked, placebo-controlled trial in type-2 diabetes was to assess the effect of the PKC beta-specific inhibitor, ruboxistaurin (32 mg/day for 6 weeks) on ultrasound assessed brachial artery flow mediated dilatation (FMD), a surrogate of macro vascular endothelial function, and urinary isoprostanes, indices of oxidant stress.	ruboxistaurin	146-159	protein kinase C beta	Homo sapiens	117-125
18485142-5	2008	In numerous experimental and clinical studies, inhibition of PKC (LY333531) has been shown to delay/halt the progression of diabetic complications.	ruboxistaurin	66-74	proline rich transmembrane protein 2	Homo sapiens	61-64
18214957-3	2008	Ruboxistaurin is a specific inhibitor of PKC-beta.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	41-49
18214957-4	2008	To understand the molecular determinants for the selectivity of ruboxistaurin, we derived the three-dimensional structures of the kinase domains of PKC-alpha, -betaI, and -zeta using homology modeling.	ruboxistaurin	64-77	protein kinase C alpha	Homo sapiens	148-157
18214957-5	2008	Several binding orientations of ruboxistaurin in the binding sites of these PKC catalytic domains were analyzed, and a putative alternative binding site for PKC-zeta was identified in its kinase domain.	ruboxistaurin	32-45	protein kinase C alpha	Homo sapiens	76-79
18214957-5	2008	Several binding orientations of ruboxistaurin in the binding sites of these PKC catalytic domains were analyzed, and a putative alternative binding site for PKC-zeta was identified in its kinase domain.	ruboxistaurin	32-45	protein kinase C zeta	Homo sapiens	157-165
18594783-6	2008	RESULTS: cPKC inhibitors RO318220, GO6976, LY333531 and CGP53353 inhibited LPS and PMA-induced expression of TTP protein and mRNA.	ruboxistaurin	43-51	ZFP36 ring finger protein	Homo sapiens	109-112
17720889-7	2007	The oral PKC inhibitor midostaurin and oral selective PKC beta inhibitor ruboxistaurin appear promising for improving or maintaining visual acuity, with gastrointestinal complaints the most commonly reported adverse effects.	ruboxistaurin	73-86	protein kinase C beta	Homo sapiens	54-62
18054736-3	2007	A new potential therapeutic agent, the PKC-beta inhibitor ruboxistaurin, has been studied in animal and human clinical trials in diabetic microvascular disease, particularly in patients with diabetic retinopathy.	ruboxistaurin	58-71	protein kinase C beta	Homo sapiens	39-47
18245560-3	2008	Homozygous PKCbeta-null (PKCbeta(-/-)) and wild-type mice fed the PKCbeta inhibitor ruboxistaurin displayed significantly decreased infarct size and enhanced recovery of left ventricular (LV) function and reduced markers of cellular necrosis and serum creatine phosphokinase and lactate dehydrogenase levels compared with wild-type or vehicle-treated animals after 30 min of ischemia followed by 48 h of reperfusion.	ruboxistaurin	84-97	protein kinase C, beta	Mus musculus	11-37
18245560-3	2008	Homozygous PKCbeta-null (PKCbeta(-/-)) and wild-type mice fed the PKCbeta inhibitor ruboxistaurin displayed significantly decreased infarct size and enhanced recovery of left ventricular (LV) function and reduced markers of cellular necrosis and serum creatine phosphokinase and lactate dehydrogenase levels compared with wild-type or vehicle-treated animals after 30 min of ischemia followed by 48 h of reperfusion.	ruboxistaurin	84-97	protein kinase C, beta	Mus musculus	11-18
17711990-5	2007	Inhibition of protein kinase C (PKC)-beta(1) with the specific pharmacological inhibitor LY-333531 or inhibition of PKC-zeta with a cell permeable specific pseudosubstrate peptide also prevented enhanced VEGF expression in high glucose.	ruboxistaurin	89-98	protein kinase C, beta	Rattus norvegicus	32-35
17711990-5	2007	Inhibition of protein kinase C (PKC)-beta(1) with the specific pharmacological inhibitor LY-333531 or inhibition of PKC-zeta with a cell permeable specific pseudosubstrate peptide also prevented enhanced VEGF expression in high glucose.	ruboxistaurin	89-98	vascular endothelial growth factor A	Rattus norvegicus	204-208
19885168-11	2007	Ruboxistaurin is able to suppress this monocyte adhesion even in a PKC beta-specific concentration.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	67-75
17522264-1	2007	Ruboxistaurin is an inhibitor of the beta isoform of protein kinase C (PKC-beta) that reduces the actions of vascular endothelial growth factor (VEGF) and attenuates the progression of diabetic retinopathy.	ruboxistaurin	0-13	protein kinase C, beta	Rattus norvegicus	71-79
17522264-1	2007	Ruboxistaurin is an inhibitor of the beta isoform of protein kinase C (PKC-beta) that reduces the actions of vascular endothelial growth factor (VEGF) and attenuates the progression of diabetic retinopathy.	ruboxistaurin	0-13	vascular endothelial growth factor A	Rattus norvegicus	109-143
17522264-1	2007	Ruboxistaurin is an inhibitor of the beta isoform of protein kinase C (PKC-beta) that reduces the actions of vascular endothelial growth factor (VEGF) and attenuates the progression of diabetic retinopathy.	ruboxistaurin	0-13	vascular endothelial growth factor A	Rattus norvegicus	145-149
17522264-8	2007	Both cell loss and VEGF overexpression were attenuated by the administration of either perindopril or ruboxistaurin, as single agent treatments with their combination providing additional, incremental improvements, reducing these manifestations of injury down to levels seen in nondiabetic, normotensive, nontransgenic animals.	ruboxistaurin	102-115	vascular endothelial growth factor A	Rattus norvegicus	19-23
16672634-6	2006	Ruboxistaurin, a PKCbeta isoform inhibitor, in the latter 2 wk of a 4-wk study, normalized vascular permeability in fat and decreased total wt gain, H2O content, and wt of fat vs. RSG alone but did not decrease VEGF expression, basal permeability, or food intake.	ruboxistaurin	0-13	protein kinase C, beta	Mus musculus	17-24
17363743-4	2007	Surprisingly, both ruboxistaurin and ACE inhibitors improved the metabolic gene profile (confirmed by real-time RT-PCR and protein analysis) and ameliorated PKC activity in diabetic hearts without altering circulating metabolites.	ruboxistaurin	19-32	protein kinase C, beta	Rattus norvegicus	157-160
17160912-5	2006	A highly selective and orally active PKC-beta isoform-selective inhibitor, ruboxistaurin, has been developed.	ruboxistaurin	75-88	protein kinase C beta	Homo sapiens	37-45
17044810-0	2006	Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin.	ruboxistaurin	53-66	protein kinase C beta	Homo sapiens	33-41
17044810-1	2006	The aim of this manuscript is to report the safety profile of patients treated with ruboxistaurin mesylate (RBX; LY333531), a selective protein kinase C-beta (PKC-beta) inhibitor, for up to 4 years.	ruboxistaurin	113-121	protein kinase C beta	Homo sapiens	136-157
17044810-1	2006	The aim of this manuscript is to report the safety profile of patients treated with ruboxistaurin mesylate (RBX; LY333531), a selective protein kinase C-beta (PKC-beta) inhibitor, for up to 4 years.	ruboxistaurin	113-121	protein kinase C beta	Homo sapiens	159-167
17504923-1	2007	To assess the role of protein kinase Cbeta (PKCbeta) in human myometrial contractions during pregnancy, we evaluated the effect of a PKCbeta inhibitor (LY333531) on the pregnant and nonpregnant myometrial contractions and compared the level of PKCbeta in the pregnant myometrium with that in the nonpregnant myometrium.	ruboxistaurin	152-160	protein kinase C beta	Homo sapiens	133-140
17504923-1	2007	To assess the role of protein kinase Cbeta (PKCbeta) in human myometrial contractions during pregnancy, we evaluated the effect of a PKCbeta inhibitor (LY333531) on the pregnant and nonpregnant myometrial contractions and compared the level of PKCbeta in the pregnant myometrium with that in the nonpregnant myometrium.	ruboxistaurin	152-160	protein kinase C beta	Homo sapiens	133-140
17472415-1	2007	Ruboxistaurin, an orally active protein kinase C beta (PKC beta) inhibitor, is a macrocyclic bisindolylmaleimide compound under development by Eli Lilly with potential as a therapy for diabetic macular oedema and other diabetic angiopathies, including diabetic retinopathy, diabetic peripheral neuropathy and diabetic nephropathy.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	55-63
16989901-1	2006	OBJECTIVE: To evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes.	ruboxistaurin	37-50	protein kinase C beta	Homo sapiens	98-106
17084284-3	2006	This review details the evidence that the protein kinase C (PKC) beta/early growth response-1 axis plays a central role in the response to both acute and chronic vascular stresses in animal models and also indicates the clinical implications of a specific inhibitor of PKCbeta, ruboxistaurin (LY333531).	ruboxistaurin	278-291	protein kinase C beta	Homo sapiens	42-69
17084284-3	2006	This review details the evidence that the protein kinase C (PKC) beta/early growth response-1 axis plays a central role in the response to both acute and chronic vascular stresses in animal models and also indicates the clinical implications of a specific inhibitor of PKCbeta, ruboxistaurin (LY333531).	ruboxistaurin	293-301	protein kinase C beta	Homo sapiens	42-69
17084284-3	2006	This review details the evidence that the protein kinase C (PKC) beta/early growth response-1 axis plays a central role in the response to both acute and chronic vascular stresses in animal models and also indicates the clinical implications of a specific inhibitor of PKCbeta, ruboxistaurin (LY333531).	ruboxistaurin	293-301	protein kinase C beta	Homo sapiens	269-276
16896067-1	2006	Ruboxistaurin is a potent and specific inhibitor of the beta isoforms of protein kinase C (PKC) that is being developed for the treatment of diabetic microvascular complications.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	91-94
16896067-8	2006	The major route of ruboxistaurin metabolism was to the N-desmethyl ruboxistaurin metabolite (LY338522), which has been shown to be active and equipotent to ruboxistaurin in the inhibition of PKC(beta).	ruboxistaurin	19-32	protein kinase C beta	Homo sapiens	191-200
16626305-13	2006	Pretreatment of cells with LY333531, a PKCbeta inhibitor, abolished Hcy-induced superoxide anion production.	ruboxistaurin	27-35	protein kinase C beta	Homo sapiens	39-46
16891764-0	2006	Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats.	ruboxistaurin	32-40	protein kinase C, beta	Rattus norvegicus	0-21
16891764-0	2006	Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats.	ruboxistaurin	32-40	intercellular adhesion molecule 1	Rattus norvegicus	52-85
16891764-0	2006	Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats.	ruboxistaurin	32-40	C-C motif chemokine ligand 2	Rattus norvegicus	90-120
16891764-2	2006	Streptozotocin-induced diabetic rats were treated with the PKC-beta isoform inhibitor LY333531 for 8 weeks.	ruboxistaurin	86-94	protein kinase C, beta	Rattus norvegicus	59-67
16891764-3	2006	LY333531 treatment significantly attenuated increased urinary albumin excretion rate and glomerular volume and tubulointerstitial injury index as well as elevated PKC activity and PKC-beta protein expression in the kidney.	ruboxistaurin	0-8	protein kinase C, beta	Rattus norvegicus	163-166
16891764-3	2006	LY333531 treatment significantly attenuated increased urinary albumin excretion rate and glomerular volume and tubulointerstitial injury index as well as elevated PKC activity and PKC-beta protein expression in the kidney.	ruboxistaurin	0-8	protein kinase C, beta	Rattus norvegicus	180-188
16891764-6	2006	Increased macrophages recruitment as well as ICAM-1 and MCP-1 protein expression in the kidney were significantly inhibited by LY333531 in diabetic rats.	ruboxistaurin	127-135	intercellular adhesion molecule 1	Rattus norvegicus	45-51
16891764-6	2006	Increased macrophages recruitment as well as ICAM-1 and MCP-1 protein expression in the kidney were significantly inhibited by LY333531 in diabetic rats.	ruboxistaurin	127-135	C-C motif chemokine ligand 2	Rattus norvegicus	56-61
16891764-7	2006	It is concluded that mechanism of renoprotection of LY333531 may be correlated, at least partly, with suppression of increased macrophages recruitment and overexpression of ICAM-1 and MCP-1 in diabetic rats.	ruboxistaurin	52-60	intercellular adhesion molecule 1	Rattus norvegicus	173-179
16891764-7	2006	It is concluded that mechanism of renoprotection of LY333531 may be correlated, at least partly, with suppression of increased macrophages recruitment and overexpression of ICAM-1 and MCP-1 in diabetic rats.	ruboxistaurin	52-60	C-C motif chemokine ligand 2	Rattus norvegicus	184-189
16672634-6	2006	Ruboxistaurin, a PKCbeta isoform inhibitor, in the latter 2 wk of a 4-wk study, normalized vascular permeability in fat and decreased total wt gain, H2O content, and wt of fat vs. RSG alone but did not decrease VEGF expression, basal permeability, or food intake.	ruboxistaurin	0-13	vascular endothelial growth factor A	Mus musculus	211-215
16564096-8	2006	In primary splenic B cells, LY333531 inhibited BCR-induced B cell proliferation, but did not affect basal or LPS-induced proliferation.	ruboxistaurin	28-36	BCR activator of RhoGEF and GTPase	Mus musculus	47-50
15822057-9	2005	Ruboxistaurin is an inhibitor of protein kinase C beta (PKC-beta), a mediator of signal transduction that leads to cell growth, fibrosis, and tissue injury.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	33-54
16505232-4	2006	Insulin-stimulated increases in Akt phosphorylation and cGMP concentration (a measure of NO bioavailability) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKCbeta inhibitor ruboxistaurin (LY333531).	ruboxistaurin	289-302	AKT serine/threonine kinase 1	Rattus norvegicus	32-35
16505232-4	2006	Insulin-stimulated increases in Akt phosphorylation and cGMP concentration (a measure of NO bioavailability) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKCbeta inhibitor ruboxistaurin (LY333531).	ruboxistaurin	304-312	AKT serine/threonine kinase 1	Rattus norvegicus	32-35
16433874-13	2006	CONCLUSIONS: The effect of rifampicin co-administration on the exposure of ruboxistaurin is consistent with ruboxistaurin being a substrate of CYP3A4.	ruboxistaurin	108-121	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	143-149
16509761-1	2006	BACKGROUND: Ruboxistaurin, a specific inhibitor of the beta(1) and beta(2) isoforms of protein kinase C, is currently in clinical development for the treatment of several diabetic microvascular complications.	ruboxistaurin	12-25	potassium calcium-activated channel subfamily M regulatory beta subunit 1	Homo sapiens	55-62
16509761-1	2006	BACKGROUND: Ruboxistaurin, a specific inhibitor of the beta(1) and beta(2) isoforms of protein kinase C, is currently in clinical development for the treatment of several diabetic microvascular complications.	ruboxistaurin	12-25	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	67-74
16384948-0	2006	Inhibition of PKC beta by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients.	ruboxistaurin	49-62	protein kinase C beta	Homo sapiens	14-22
16384948-1	2006	PURPOSE: To assess ocular and systemic safety and pharmacodynamic effects of the oral PKC beta selective inhibitor ruboxistaurin (RBX; LY333531) mesylate in patients with diabetes.	ruboxistaurin	115-128	protein kinase C beta	Homo sapiens	86-94
16384948-1	2006	PURPOSE: To assess ocular and systemic safety and pharmacodynamic effects of the oral PKC beta selective inhibitor ruboxistaurin (RBX; LY333531) mesylate in patients with diabetes.	ruboxistaurin	130-133	protein kinase C beta	Homo sapiens	86-94
16564096-7	2006	Treatment of Daudi B lymphoma cell line with a selective PKCbeta inhibitor, LY333531, inhibited anti-IgM-induced phosphorylation of BTK on Ser180 in a concentration-dependent manner, which was concomitant with an increase in BTK activation, and Ca2+ mobilization.	ruboxistaurin	76-84	protein kinase C beta	Homo sapiens	57-64
16564096-7	2006	Treatment of Daudi B lymphoma cell line with a selective PKCbeta inhibitor, LY333531, inhibited anti-IgM-induced phosphorylation of BTK on Ser180 in a concentration-dependent manner, which was concomitant with an increase in BTK activation, and Ca2+ mobilization.	ruboxistaurin	76-84	Bruton tyrosine kinase	Homo sapiens	132-135
16564096-7	2006	Treatment of Daudi B lymphoma cell line with a selective PKCbeta inhibitor, LY333531, inhibited anti-IgM-induced phosphorylation of BTK on Ser180 in a concentration-dependent manner, which was concomitant with an increase in BTK activation, and Ca2+ mobilization.	ruboxistaurin	76-84	Bruton tyrosine kinase	Homo sapiens	225-228
16433874-0	2006	Pharmacokinetics of ruboxistaurin are significantly altered by rifampicin-mediated CYP3A4 induction.	ruboxistaurin	20-33	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	83-89
16160002-1	2005	OBJECTIVE: To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) beta, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications.	ruboxistaurin	82-95	protein kinase C beta	Homo sapiens	133-160
16160002-1	2005	OBJECTIVE: To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) beta, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications.	ruboxistaurin	97-105	protein kinase C beta	Homo sapiens	133-160
16160002-7	2005	CONCLUSIONS: Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes.	ruboxistaurin	13-26	protein kinase C beta	Homo sapiens	83-86
15822057-9	2005	Ruboxistaurin is an inhibitor of protein kinase C beta (PKC-beta), a mediator of signal transduction that leads to cell growth, fibrosis, and tissue injury.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	56-64
15662033-2	2005	Homozygous PKCbeta null (-/-) mice or wild-type mice fed the PKCbeta inhibitor, ruboxistaurin, displayed significantly decreased neointimal expansion in response to acute femoral artery endothelial denudation injury compared with controls.	ruboxistaurin	80-93	protein kinase C, beta	Mus musculus	11-18
15662033-2	2005	Homozygous PKCbeta null (-/-) mice or wild-type mice fed the PKCbeta inhibitor, ruboxistaurin, displayed significantly decreased neointimal expansion in response to acute femoral artery endothelial denudation injury compared with controls.	ruboxistaurin	80-93	protein kinase C, beta	Mus musculus	61-68
15539624-11	2005	Importantly, IL-8 significantly induced CRP release in PHHs by 58.675+/-19.1-fold, which was blockable by LY333531.	ruboxistaurin	106-114	C-X-C motif chemokine ligand 8	Homo sapiens	13-17
15539624-11	2005	Importantly, IL-8 significantly induced CRP release in PHHs by 58.675+/-19.1-fold, which was blockable by LY333531.	ruboxistaurin	106-114	C-reactive protein	Homo sapiens	40-43
15067074-7	2004	Finally, nuclear run-on assays demonstrated that while the PKC inhibitors, Go6976 and LY333531, decrease the IFN-gamma-induced gp91(phox) transcription, the serine phosphatase inhibitor, okadaic acid, enhances the gp91(phox) gene transcription.	ruboxistaurin	86-94	interferon gamma	Homo sapiens	109-118
15140758-7	2004	Inhibition of PKC-beta with 100 nM ruboxistaurin prevented eNOS suppression in high-glucose media.	ruboxistaurin	35-48	protein kinase C, beta	Mus musculus	14-22
15140758-7	2004	Inhibition of PKC-beta with 100 nM ruboxistaurin prevented eNOS suppression in high-glucose media.	ruboxistaurin	35-48	nitric oxide synthase 3, endothelial cell	Mus musculus	59-63
15173888-3	2004	Homozygous PKCbeta-null mice and WT mice fed the PKCbeta inhibitor ruboxistaurin subjected to I/R displayed increased survival compared with controls.	ruboxistaurin	67-80	protein kinase C, beta	Mus musculus	11-18
15173888-3	2004	Homozygous PKCbeta-null mice and WT mice fed the PKCbeta inhibitor ruboxistaurin subjected to I/R displayed increased survival compared with controls.	ruboxistaurin	67-80	protein kinase C, beta	Mus musculus	49-56
15173888-5	2004	Expression of the immediate early gene, early growth response-1 (Egr-1), and its downstream target genes was significantly increased in WT mice in I/R, particularly in mononuclear phagocytes (MPs), whereas this expression was attenuated in PKCbeta-null mice or WT mice fed ruboxistaurin.	ruboxistaurin	273-286	early growth response 1	Mus musculus	40-63
15173888-5	2004	Expression of the immediate early gene, early growth response-1 (Egr-1), and its downstream target genes was significantly increased in WT mice in I/R, particularly in mononuclear phagocytes (MPs), whereas this expression was attenuated in PKCbeta-null mice or WT mice fed ruboxistaurin.	ruboxistaurin	273-286	early growth response 1	Mus musculus	65-70
14715497-4	2004	Ruboxistaurin (LY-333531) was used to inhibit PKC-betaII to determine whether flow or oxygen-related NO regulation was improved.	ruboxistaurin	0-13	phospholipase C, beta 2	Rattus norvegicus	46-56
15067074-6	2004	Moreover, we found that the treatment of monocytes with IFN-gamma induces the nuclear translocation and the activation of PKC alpha and beta I, but not of PKC beta II, and that the IFN-gamma-induced phosphorylation of PU.1 was greatly reduced by LY333531, a selective inhibitor of PKC beta isoforms.	ruboxistaurin	246-254	interferon gamma	Homo sapiens	56-65
15067074-6	2004	Moreover, we found that the treatment of monocytes with IFN-gamma induces the nuclear translocation and the activation of PKC alpha and beta I, but not of PKC beta II, and that the IFN-gamma-induced phosphorylation of PU.1 was greatly reduced by LY333531, a selective inhibitor of PKC beta isoforms.	ruboxistaurin	246-254	interferon gamma	Homo sapiens	181-190
15067074-7	2004	Finally, nuclear run-on assays demonstrated that while the PKC inhibitors, Go6976 and LY333531, decrease the IFN-gamma-induced gp91(phox) transcription, the serine phosphatase inhibitor, okadaic acid, enhances the gp91(phox) gene transcription.	ruboxistaurin	86-94	protein kinase C alpha	Homo sapiens	59-62
14715497-4	2004	Ruboxistaurin (LY-333531) was used to inhibit PKC-betaII to determine whether flow or oxygen-related NO regulation was improved.	ruboxistaurin	15-24	phospholipase C, beta 2	Rattus norvegicus	46-56
14581181-6	2003	LY333531 (1 microM), a specific inhibitor of PKC beta, also inhibited the PDBu-induced contraction in the pregnant myometrium.	ruboxistaurin	0-8	protein kinase C beta	Homo sapiens	45-53
14962382-0	2004	Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1.	ruboxistaurin	16-24	pyruvate dehydrogenase kinase 1	Homo sapiens	72-76
12954365-2	2003	Treatment with the PKCbeta inhibitor, (s)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-dione, (LY333531), improves somatic nerve function and blood flow in diabetic rats.	ruboxistaurin	193-201	protein kinase C, beta	Rattus norvegicus	19-26
12955673-4	2003	Ruboxistaurin (LY333531) mesylate is a bisindolylmaleimide that shows a high degree of specificity within the protein kinase C (PKC) gene family for inhibiting PKC beta isoforms.	ruboxistaurin	0-13	protein kinase C, beta	Rattus norvegicus	128-131
12955673-4	2003	Ruboxistaurin (LY333531) mesylate is a bisindolylmaleimide that shows a high degree of specificity within the protein kinase C (PKC) gene family for inhibiting PKC beta isoforms.	ruboxistaurin	0-13	protein kinase C, beta	Rattus norvegicus	160-168
12955673-4	2003	Ruboxistaurin (LY333531) mesylate is a bisindolylmaleimide that shows a high degree of specificity within the protein kinase C (PKC) gene family for inhibiting PKC beta isoforms.	ruboxistaurin	15-24	protein kinase C, beta	Rattus norvegicus	128-131
12955673-4	2003	Ruboxistaurin (LY333531) mesylate is a bisindolylmaleimide that shows a high degree of specificity within the protein kinase C (PKC) gene family for inhibiting PKC beta isoforms.	ruboxistaurin	15-24	protein kinase C, beta	Rattus norvegicus	160-168
12955673-5	2003	In animal models of diabetes, including the streptozotocin (STZ) rat, Lepr(db)/Lepr(db) mouse, and STZ-Ren 2 rat models, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, and reduced glomerular transforming growth factor-beta1 and extracellular matrix protein production.	ruboxistaurin	121-134	leptin receptor	Rattus norvegicus	70-74
12955673-5	2003	In animal models of diabetes, including the streptozotocin (STZ) rat, Lepr(db)/Lepr(db) mouse, and STZ-Ren 2 rat models, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, and reduced glomerular transforming growth factor-beta1 and extracellular matrix protein production.	ruboxistaurin	121-134	leptin receptor	Rattus norvegicus	79-83
12955673-5	2003	In animal models of diabetes, including the streptozotocin (STZ) rat, Lepr(db)/Lepr(db) mouse, and STZ-Ren 2 rat models, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, and reduced glomerular transforming growth factor-beta1 and extracellular matrix protein production.	ruboxistaurin	121-134	transforming growth factor, beta 1	Rattus norvegicus	234-266
14683472-7	2003	Recent studies demonstrated that LY333531, a PKC-beta-specific inhibitor, reduced the development of diabetic vascular complications in animal models and prevented hyperglycemia-induced impairment of endothelial-dependent vasodilation in healthy subjects.	ruboxistaurin	33-41	protein kinase C beta	Homo sapiens	45-53
14514646-4	2003	Urinary 8-hydroxydeoxyguanosine excretion and its intense immune-reactive staining in the glomeruli were markedly higher in diabetic than in control rats, and these alterations were ameliorated by a treatment with a selective PKC-beta inhibitor, ruboxistaurin (RBX; LY333531) mesylate, without affecting glycemia.	ruboxistaurin	246-259	protein kinase C, beta	Rattus norvegicus	226-234
14514646-4	2003	Urinary 8-hydroxydeoxyguanosine excretion and its intense immune-reactive staining in the glomeruli were markedly higher in diabetic than in control rats, and these alterations were ameliorated by a treatment with a selective PKC-beta inhibitor, ruboxistaurin (RBX; LY333531) mesylate, without affecting glycemia.	ruboxistaurin	261-264	protein kinase C, beta	Rattus norvegicus	226-234
14514646-4	2003	Urinary 8-hydroxydeoxyguanosine excretion and its intense immune-reactive staining in the glomeruli were markedly higher in diabetic than in control rats, and these alterations were ameliorated by a treatment with a selective PKC-beta inhibitor, ruboxistaurin (RBX; LY333531) mesylate, without affecting glycemia.	ruboxistaurin	266-274	protein kinase C, beta	Rattus norvegicus	226-234
12882929-9	2003	These results suggest that LY is effective for treating diabetic hyperalgesia through ameliorating the decrease in the nNOS-cGMP system.	ruboxistaurin	27-29	nitric oxide synthase 1	Rattus norvegicus	119-123
12203947-2	2002	Neuropathy has a vascular component; therefore, one aim was to assess whether the PKCbeta inhibitor, LY333531, could correct nerve conduction velocity (NCV) and perfusion deficits in diabetic rats.	ruboxistaurin	101-109	protein kinase C, beta	Rattus norvegicus	82-89
12789620-1	2003	Eli Lilly & Co is developing the protein kinase C (PKC)-b inhibitor ruboxistaurin, the lead compound from a series of 14-membered macrocycles, for the potential treatment of diabetic retinopathy, diabetic peripheral neuropathy and macular edema.	ruboxistaurin	72-85	protein kinase C beta	Homo sapiens	37-61
12507628-10	2002	Studies suggest that orally administered LY333531, a beta-isoform specific PKC inhibitor, may be effective in ameliorating retinopathy progression, proliferation, and retinal vascular leakage.	ruboxistaurin	41-49	protein kinase C beta	Homo sapiens	75-78
12606528-4	2003	Treatment with PKC-beta isoform-specific inhibitor (LY333531) or insulin normalized retinal ET-1 and PDGF-B expression.	ruboxistaurin	52-60	protein kinase C, beta	Rattus norvegicus	15-23
12606528-4	2003	Treatment with PKC-beta isoform-specific inhibitor (LY333531) or insulin normalized retinal ET-1 and PDGF-B expression.	ruboxistaurin	52-60	endothelin 1	Rattus norvegicus	92-96
12606528-4	2003	Treatment with PKC-beta isoform-specific inhibitor (LY333531) or insulin normalized retinal ET-1 and PDGF-B expression.	ruboxistaurin	52-60	platelet derived growth factor subunit B	Rattus norvegicus	101-107
12540629-6	2003	Within 24 h, diabetic rats were further randomized to receive treatment with the specific PKC beta inhibitor, LY333531, admixed in diet (10 mg x kg(-1) x d(-1)) or no treatment (n = 8/group).	ruboxistaurin	110-118	protein kinase C, beta	Rattus norvegicus	90-98
12540629-9	2003	In vivo inhibition of PKC beta with LY333531 led to a reduction in albuminuria, structural injury, and TGF-beta expression, despite continued hypertension and hyperglycemia.	ruboxistaurin	36-44	protein kinase C, beta	Rattus norvegicus	22-30
12167559-5	2002	Of the nine cDNA-expressed P450s examined, only CYP3A4 and CYP2D6 formed N-desmethyl LY333531.	ruboxistaurin	85-93	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	48-54
12167559-5	2002	Of the nine cDNA-expressed P450s examined, only CYP3A4 and CYP2D6 formed N-desmethyl LY333531.	ruboxistaurin	85-93	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	59-65
12167559-9	2002	LY333531 and N-desmethyl LY333531 were also examined for their ability to inhibit metabolism mediated by CYP2D6, CYP2C9, CYP3A, and CYP1A2.	ruboxistaurin	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	105-111
12167559-9	2002	LY333531 and N-desmethyl LY333531 were also examined for their ability to inhibit metabolism mediated by CYP2D6, CYP2C9, CYP3A, and CYP1A2.	ruboxistaurin	0-8	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	113-119
12167559-9	2002	LY333531 and N-desmethyl LY333531 were also examined for their ability to inhibit metabolism mediated by CYP2D6, CYP2C9, CYP3A, and CYP1A2.	ruboxistaurin	0-8	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	121-126
12167559-10	2002	LY333531 and N-desmethyl LY333531 were found to competitively inhibit CYP2D6 with calculated K(i) values of 0.17 and 1.0 microM, respectively.	ruboxistaurin	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	70-76
12167559-14	2002	In addition, LY333531 and its metabolite are predicted to be potential inhibitors of CYP2D6-mediated reactions in vivo.	ruboxistaurin	13-21	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	85-91
11855796-5	2001	Addition of N-acetyl cysteine, LY333531, or L-NAME significantly inhibited glucose-induced elevation in oxidative stress, NO and PKC.	ruboxistaurin	31-39	protein kinase C, gamma	Rattus norvegicus	129-132
11937071-6	2002	Inhibition of PKC with the PKC-selective inhibitor, LY333531, prevented the VPA-induced down-regulation of membrane-associated MARCKS, but had no effect on the cytosolic MARCKS reduction or the GAP-43 up-regulation.	ruboxistaurin	52-60	myristoylated alanine rich protein kinase C substrate	Homo sapiens	127-133
11855796-7	2001	In diabetic rats, elevations in retinal TBARS, PKC and NO were observed at 2 months of diabetes, and administration of N-acetyl cysteine, LY333531 or aminoguanidine prevented diabetes-induced elevation in retinal TBARS and NO levels, and PKC activity.	ruboxistaurin	138-146	protein kinase C, gamma	Rattus norvegicus	47-50
11903393-5	2001	This has lead to the development of LY333531, a PKCbeta isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction.	ruboxistaurin	36-44	protein kinase C beta	Homo sapiens	48-55
11440359-7	2001	Interventions that increase DAG metabolism (e. g. vitamin E) and/or inhibit PKC isozymes (e. g. the beta-selective inhibitor LY333531) ameliorate the biochemical and functional consequences of DAG-PKC activation in experimental diabetes, for example improving retinal blood flow and albuminuria in parallel with reductions in membrane-associated PKC isozyme activities.	ruboxistaurin	125-133	protein kinase C beta	Homo sapiens	76-79
11440359-7	2001	Interventions that increase DAG metabolism (e. g. vitamin E) and/or inhibit PKC isozymes (e. g. the beta-selective inhibitor LY333531) ameliorate the biochemical and functional consequences of DAG-PKC activation in experimental diabetes, for example improving retinal blood flow and albuminuria in parallel with reductions in membrane-associated PKC isozyme activities.	ruboxistaurin	125-133	protein kinase C beta	Homo sapiens	197-200
11440359-7	2001	Interventions that increase DAG metabolism (e. g. vitamin E) and/or inhibit PKC isozymes (e. g. the beta-selective inhibitor LY333531) ameliorate the biochemical and functional consequences of DAG-PKC activation in experimental diabetes, for example improving retinal blood flow and albuminuria in parallel with reductions in membrane-associated PKC isozyme activities.	ruboxistaurin	125-133	protein kinase C beta	Homo sapiens	197-200
11178962-2	2001	[3H]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM glucose, and this increase was inhibited by an anti-TGF-beta antibody or a PKC-beta specific inhibitor, LY333531.	ruboxistaurin	215-223	transforming growth factor beta 1	Homo sapiens	163-171
11178962-2	2001	[3H]-thymidine incorporation under 20 mM glucose was significantly accelerated compared with that under 5.5 mM glucose, and this increase was inhibited by an anti-TGF-beta antibody or a PKC-beta specific inhibitor, LY333531.	ruboxistaurin	215-223	protein kinase C beta	Homo sapiens	186-194
11178962-5	2001	This increased expression of the TGF-beta receptor type II was prevented by LY333531.	ruboxistaurin	76-84	transforming growth factor beta 1	Homo sapiens	33-41
10673261-5	2000	Inhibitors of phosphatidylinositol-3 kinase (PI-3 kinase) decreased the effect of insulin on eNOS gene expression, but a general protein kinase C (PKC) inhibitor, GF109203X or PKCbeta isoform inhibitor, LY333531 enhanced eNOS expression.	ruboxistaurin	203-211	insulin	Bos taurus	82-89
10937586-0	2000	PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats.	ruboxistaurin	20-28	protein kinase C, beta	Rattus norvegicus	0-8
10937586-2	2000	Recently, LY333531, a specific inhibitor of PKC-beta, has been reported to improve the decrease of retinal blood flow in early diabetes.	ruboxistaurin	10-18	protein kinase C, beta	Rattus norvegicus	44-52
10767572-1	2000	LY333531 is a potent protein kinase C(beta) (PKC(beta)) inhibitor currently under development for the treatment of diabetic complications.	ruboxistaurin	0-8	protein kinase C beta	Canis lupus familiaris	21-43
10767572-1	2000	LY333531 is a potent protein kinase C(beta) (PKC(beta)) inhibitor currently under development for the treatment of diabetic complications.	ruboxistaurin	0-8	protein kinase C beta	Canis lupus familiaris	45-54
10512378-3	1999	The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ).	ruboxistaurin	107-115	protein kinase C, beta	Rattus norvegicus	57-60
10512378-3	1999	The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ).	ruboxistaurin	107-115	protein kinase C, beta	Rattus norvegicus	77-85
10512378-3	1999	The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ).	ruboxistaurin	107-109	protein kinase C, beta	Rattus norvegicus	57-60
10512378-3	1999	The present study was conducted to compare the effect of PKC inhibition by a PKC-beta-selective inhibitor, LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ).	ruboxistaurin	107-109	protein kinase C, beta	Rattus norvegicus	77-85
10512378-10	1999	These observations suggest that inhibition of PKC-beta by LY may have a beneficial effect in preventing the development of diabetic nerve dysfunction, and that this effect may be mediated through its action on the endoneurial micro-vasculature.	ruboxistaurin	58-60	protein kinase C, beta	Rattus norvegicus	46-54
10452527-3	1999	LY333531, a specific inhibitor of the PKC-beta isoform, prevents PMA-dependent activation of Na+,K+-ATPase, but has no effect on DA inhibition of this activity.	ruboxistaurin	0-8	protein kinase C beta	Homo sapiens	38-46
10485491-6	1999	In this study, we combined this Retro-tet system and LY333531, an inhibitor of the PKC-beta isoform, to elucidate the role of PKC-beta in tumor development and angiogenesis.	ruboxistaurin	53-61	protein kinase C beta	Homo sapiens	83-91
9462865-7	1998	In addition, the inhibition of PKC beta isoforms by a specific inhibitor (LY333531) can normalize the changes in gene expression of cytokines, caldesmon, and hemodynamics.	ruboxistaurin	74-82	protein kinase C, beta	Rattus norvegicus	31-39
9418723-12	1997	Intravitreal injection of the PKC-beta inhibitor (LY333531) at 10(-5) M in diabetic rats decreased by a factor of 1.6 the diabetes-related increased PKC activation, decreased the prolonged MCT (0.98 +/- 0.13 seconds; P < 0.01) and increased retinal blood flow (93.4 +/- 14.2 pixel2/second; P < 0.01).	ruboxistaurin	50-58	protein kinase C, beta	Rattus norvegicus	30-38
9418723-12	1997	Intravitreal injection of the PKC-beta inhibitor (LY333531) at 10(-5) M in diabetic rats decreased by a factor of 1.6 the diabetes-related increased PKC activation, decreased the prolonged MCT (0.98 +/- 0.13 seconds; P < 0.01) and increased retinal blood flow (93.4 +/- 14.2 pixel2/second; P < 0.01).	ruboxistaurin	50-58	protein kinase C, beta	Rattus norvegicus	30-33
10470381-1	1999	The macrocyclic bisindolylmaleimide, LY333531, selectively inhibits protein kinase C beta 1 and beta 2 isoforms with an approximate IC50 of 5 nanomolar.	ruboxistaurin	37-45	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	96-102
9519755-4	1998	Diabetes or experimental galactosemia of 2 months" duration resulted in > 50% elevation of PKC activity in the retina, and administration of LY333531 prevented the elevation.	ruboxistaurin	144-152	protein kinase C, gamma	Rattus norvegicus	94-97
9519755-6	1998	Retinal microvessels, the main site of lesions in diabetic retinopathy, likewise showed elevated activity of PKC and inhibition of ATPases in diabetes and in experimental galactosemia, and administration of LY333531 to diabetic animals prevented these abnormalities.	ruboxistaurin	207-215	protein kinase C, gamma	Rattus norvegicus	109-112
8709095-8	1996	LY333531 (1) exhibits ATP dependent competitive inhibition of PKC beta I and is selective for PKC in comparison to other ATP dependent kinases (protein kinase A, calcium calmodulin, caesin kinase, src tyrosine kinase).	ruboxistaurin	0-8	protein kinase C beta	Homo sapiens	62-70
9202063-2	1997	Recently, we have reported that the use of a novel, orally effective specific inhibitor of PKC beta isoform (LY333531) normalized many of the early retinal and renal hemodynamics in rat models of diabetes.	ruboxistaurin	109-117	protein kinase C, beta	Rattus norvegicus	91-99
9202063-5	1997	The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation.	ruboxistaurin	46-54	protein kinase C, beta	Rattus norvegicus	16-24
9202063-5	1997	The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation.	ruboxistaurin	46-54	protein kinase C, alpha	Rattus norvegicus	16-19
9202063-5	1997	The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation.	ruboxistaurin	46-54	protein kinase C, alpha	Rattus norvegicus	284-293
9202063-5	1997	The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation.	ruboxistaurin	167-175	protein kinase C, beta	Rattus norvegicus	16-24
9202063-5	1997	The addition of PKC beta selective inhibitor (LY333531) to cultured mesangial cells inhibited activated PKC activities by high glucose without lowering DAG levels and LY333531 given orally in diabetic rats specifically inhibited the activation of PKC beta1 isoform without decreasing PKC alpha isoform activation.	ruboxistaurin	167-175	protein kinase C, alpha	Rattus norvegicus	284-293
9202063-7	1997	Oral feeding of LY333531 prevented the increased mRNA expression of TGF-beta1 and extracellular matrix components such as fibronectin and alpha1(IV) collagen in the glomeruli of diabetic rats in parallel with inhibition of glomerular PKC activity.	ruboxistaurin	16-24	transforming growth factor, beta 1	Rattus norvegicus	68-77
9202063-7	1997	Oral feeding of LY333531 prevented the increased mRNA expression of TGF-beta1 and extracellular matrix components such as fibronectin and alpha1(IV) collagen in the glomeruli of diabetic rats in parallel with inhibition of glomerular PKC activity.	ruboxistaurin	16-24	fibronectin 1	Rattus norvegicus	122-133
9202063-7	1997	Oral feeding of LY333531 prevented the increased mRNA expression of TGF-beta1 and extracellular matrix components such as fibronectin and alpha1(IV) collagen in the glomeruli of diabetic rats in parallel with inhibition of glomerular PKC activity.	ruboxistaurin	16-24	protein kinase C, alpha	Rattus norvegicus	234-237
8903320-9	1996	VEGF"s mitogenic effect was inhibited by a PKC isoform beta-selective inhibitor, LY333531, in a concentration-dependent manner.	ruboxistaurin	81-89	vascular endothelial growth factor A	Bos taurus	0-4
8903320-9	1996	VEGF"s mitogenic effect was inhibited by a PKC isoform beta-selective inhibitor, LY333531, in a concentration-dependent manner.	ruboxistaurin	81-89	protein kinase C alpha	Bos taurus	43-46
8709095-8	1996	LY333531 (1) exhibits ATP dependent competitive inhibition of PKC beta I and is selective for PKC in comparison to other ATP dependent kinases (protein kinase A, calcium calmodulin, caesin kinase, src tyrosine kinase).	ruboxistaurin	0-8	protein kinase C alpha	Homo sapiens	62-65
34560214-11	2022	After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats.	ruboxistaurin	70-78	protein kinase C, alpha	Rattus norvegicus	259-262
8614835-2	1996	LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory constant of approximately 5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases.	ruboxistaurin	0-8	protein kinase C, beta	Rattus norvegicus	54-57
8614835-2	1996	LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory constant of approximately 5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases.	ruboxistaurin	0-8	protein kinase C, beta	Rattus norvegicus	133-141
8614835-2	1996	LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory constant of approximately 5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases.	ruboxistaurin	0-8	protein kinase C, beta	Rattus norvegicus	133-136
8614835-2	1996	LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory constant of approximately 5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases.	ruboxistaurin	0-8	protein kinase C, beta	Rattus norvegicus	133-136
8614835-3	1996	When administered orally, LY333531 ameliorated the glomerular filtration rate, albumin excretion rate, and retinal circulation in diabetic rats in a dose-responsive manner, in parallel with its inhibition of PKC activities.	ruboxistaurin	26-34	protein kinase C, beta	Rattus norvegicus	208-211
34474112-5	2021	METHODS: Bovine aortic endothelial cells were stimulated in vitro under pharmacological inhibition of PKCbeta with LY333531 or PKCeta targeting with a pseudosubstrate inhibitor.	ruboxistaurin	115-123	protein kinase C alpha	Bos taurus	102-109
34698097-7	2021	Ro-31-8220 and Go6976 also suppressed this upregulation, however, the PKCdelta selective inhibitor rottlerin and the PKCbeta selective inhibitor Ly333531 did not.	ruboxistaurin	145-153	protein kinase C alpha	Homo sapiens	117-124
35062863-15	2022	Administering LY333531 significantly increased the body weight of diabetic ApoE-/- mice, inhibited the immune maturation of spleen DCs, and reduced atherosclerotic plaques in diabetic ApoE-/- mice.	ruboxistaurin	14-22	apolipoprotein E	Mus musculus	75-79
35527461-3	2022	The cells were intervened by PKC agonist (PMA), PKCalpha inhibitor (safingol), PKCbetaI inhibitor (Go6976) and PKCbetaII inhibitor (LY333531) respectively, and the changes in protein expressions of cPKCs, and the phosphorylation levels of ERK1/2 and Akt were observed by immunoblotting under the condition of normal oxygen or hypoxia.	ruboxistaurin	132-140	mitogen-activated protein kinase 3	Mus musculus	239-245
35527461-3	2022	The cells were intervened by PKC agonist (PMA), PKCalpha inhibitor (safingol), PKCbetaI inhibitor (Go6976) and PKCbetaII inhibitor (LY333531) respectively, and the changes in protein expressions of cPKCs, and the phosphorylation levels of ERK1/2 and Akt were observed by immunoblotting under the condition of normal oxygen or hypoxia.	ruboxistaurin	132-140	thymoma viral proto-oncogene 1	Mus musculus	250-253
35527461-11	2022	Using Western blotting, we also observed that after being inhibited by safingol, Go6976 and LY333531 respectively, the phosphorylation levels of ERK1/2 and Akt in PASMCs induced by hypoxia was significantly lower than the control group.	ruboxistaurin	92-100	mitogen-activated protein kinase 3	Mus musculus	145-151
35527461-11	2022	Using Western blotting, we also observed that after being inhibited by safingol, Go6976 and LY333531 respectively, the phosphorylation levels of ERK1/2 and Akt in PASMCs induced by hypoxia was significantly lower than the control group.	ruboxistaurin	92-100	thymoma viral proto-oncogene 1	Mus musculus	156-159
35062863-15	2022	Administering LY333531 significantly increased the body weight of diabetic ApoE-/- mice, inhibited the immune maturation of spleen DCs, and reduced atherosclerotic plaques in diabetic ApoE-/- mice.	ruboxistaurin	14-22	apolipoprotein E	Mus musculus	184-188
32882584-8	2020	Moreover, we found that ruboxistaurin inhibited osteoclast formation and resorption activity by suppressing the expressions of osteoclast-related genes and (PKCdelta/MAPKs) signaling cascade.	ruboxistaurin	24-37	protein kinase C delta	Homo sapiens	157-165
33561320-10	2021	In vivo experiment, PKC-beta elective inhibitor LY333531 prolonged survival time in CML-PDX mice model.	ruboxistaurin	48-56	protein kinase C, alpha	Mus musculus	20-28
32544612-7	2020	In a mouse model, the selective inhibition of PKCbeta by Ruboxistaurin was sufficient to induce preeclampsia-like symptoms, accompanied by excessive autophagic flux and a disruption in the balance of pro- and anti-angiogenic factors in mouse placentas.	ruboxistaurin	57-70	protein kinase C, alpha	Mus musculus	46-53
33110983-9	2020	Subsequent testing of selected compounds revealed a selective small-molecule inhibitor, ruboxistaurin, with activity against GSK3beta (avg IC50 = 97.3 nM) and GSK3alpha (IC50 = 695.9 nM).	ruboxistaurin	88-101	glycogen synthase kinase 3 alpha	Homo sapiens	125-133
33110983-9	2020	Subsequent testing of selected compounds revealed a selective small-molecule inhibitor, ruboxistaurin, with activity against GSK3beta (avg IC50 = 97.3 nM) and GSK3alpha (IC50 = 695.9 nM).	ruboxistaurin	88-101	glycogen synthase kinase 3 alpha	Homo sapiens	159-168
33085045-5	2020	PKCbeta inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-kappaBp65, p-IkappaB, P38MARK, TNF-alpha, TGF-beta, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats.	ruboxistaurin	25-38	protein kinase C, alpha	Rattus norvegicus	0-7
33085045-5	2020	PKCbeta inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-kappaBp65, p-IkappaB, P38MARK, TNF-alpha, TGF-beta, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats.	ruboxistaurin	25-38	tumor necrosis factor	Rattus norvegicus	120-129
33085045-5	2020	PKCbeta inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-kappaBp65, p-IkappaB, P38MARK, TNF-alpha, TGF-beta, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats.	ruboxistaurin	25-38	transforming growth factor alpha	Rattus norvegicus	131-139
33085045-5	2020	PKCbeta inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-kappaBp65, p-IkappaB, P38MARK, TNF-alpha, TGF-beta, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats.	ruboxistaurin	25-38	solute carrier family 8 member A1	Rattus norvegicus	153-156
28128334-5	2017	We have therefore investigated the in vivo effects of the selective PKCbeta inhibitor, ruboxistaurin (LY-333531), in a preclinical model of long-term clozapine-induced weight gain.	ruboxistaurin	87-100	protein kinase C beta	Homo sapiens	68-75
31404587-6	2019	Diabetic animals pre-treated with Protein Kinase C (PKC)-alpha and -beta inhibitor (GO6976) or PKC-beta inhibitor (LY333531) significantly increased capsaicin-induced nociception in the TMJ higher protein levels of Na+/K+-ATPase pump in the trigeminal ganglia.	ruboxistaurin	115-123	protein kinase C, alpha	Rattus norvegicus	95-103
30921339-8	2019	In contrast, PKC inhibitors calphostin C, Go6976, sotrastaurin and ruboxistaurin suppressed FGF23 formation.	ruboxistaurin	67-80	protein kinase C, gamma	Rattus norvegicus	13-16
30921339-8	2019	In contrast, PKC inhibitors calphostin C, Go6976, sotrastaurin and ruboxistaurin suppressed FGF23 formation.	ruboxistaurin	67-80	fibroblast growth factor 23	Rattus norvegicus	92-97
28478520-3	2017	Other forty rats were assigned to SAL group, AFG group, LY group (PKCbeta inhibitor LY333531 was injected intragastrically to the rats who were under acute blood glucose fluctuation) and SP group (JNK inhibitor SP600125 was injected intraperitoneally to the rats who were under acute blood glucose fluctuation).	ruboxistaurin	84-92	protein kinase C, beta	Rattus norvegicus	66-73
28478520-7	2017	RESULTS: After administration of LY333531, AFG-induced membrane translocation of PKCbetaII protein was inhibited, but SP600125 failed to affect AFG-induced PKCbetaII membrane translocation.	ruboxistaurin	33-41	phospholipase C, beta 2	Rattus norvegicus	81-90
28478520-8	2017	After administration of LY333531, the AFG-induced increase in JNK activity was significantly compromised.	ruboxistaurin	24-32	mitogen-activated protein kinase 8	Rattus norvegicus	62-65
28414198-0	2017	LY333531, a PKCbeta inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1.	ruboxistaurin	0-8	protein kinase C, beta	Mus musculus	12-19
28414198-0	2017	LY333531, a PKCbeta inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1.	ruboxistaurin	0-8	EF hand domain containing 2	Mus musculus	149-160
28414198-5	2017	Administration of LY333531 (1 mg kg-1 d-1 for 8 weeks) significantly attenuated both GEC apoptosis and swiprosin-1 upregulation in the diabetic mice.	ruboxistaurin	18-26	EF hand domain containing 2	Mus musculus	103-114
28369981-9	2017	Vasorelaxation of SHR aortas by propofol was markedly attenuated by LY333531 (a specific PKCbeta inhibitor) or the PKCtheta pseudo-substrate inhibitor.	ruboxistaurin	68-76	protein kinase C, beta	Rattus norvegicus	89-96
32048876-6	2020	Chronic oral administration of the antioxidant Tempol or the PKCbeta inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy.	ruboxistaurin	79-88	protein kinase C, alpha	Rattus norvegicus	61-68
31785237-8	2020	In addition, we show that general PKCbeta (LY-333531) and PKCbetaII inhibitors but not PKCalpha or PKCbetaI inhibitors blocked the effect of cPKC on the KCNQ1/KCNE1 channel.	ruboxistaurin	43-52	protein kinase C beta	Homo sapiens	34-41
31785237-8	2020	In addition, we show that general PKCbeta (LY-333531) and PKCbetaII inhibitors but not PKCalpha or PKCbetaI inhibitors blocked the effect of cPKC on the KCNQ1/KCNE1 channel.	ruboxistaurin	43-52	potassium voltage-gated channel subfamily Q member 1	Homo sapiens	153-158
31785237-8	2020	In addition, we show that general PKCbeta (LY-333531) and PKCbetaII inhibitors but not PKCalpha or PKCbetaI inhibitors blocked the effect of cPKC on the KCNQ1/KCNE1 channel.	ruboxistaurin	43-52	potassium voltage-gated channel subfamily E regulatory subunit 1	Homo sapiens	159-164
30384585-4	2019	Previous works showed that the selective inhibitors of protein kinase Cbeta (PKCbeta), enzastaurin and ruboxistaurin, attenuate dopamine overflow and locomotion stimulated by another psychostimulant drug, amphetamine.	ruboxistaurin	103-116	protein kinase C, beta	Mus musculus	55-75
29440456-13	2018	The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment.	ruboxistaurin	116-129	thymoma viral proto-oncogene 1	Mus musculus	27-30
29440456-13	2018	The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment.	ruboxistaurin	116-129	thymoma viral proto-oncogene 1	Mus musculus	34-37
29440456-13	2018	The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment.	ruboxistaurin	116-129	vascular endothelial growth factor A	Mus musculus	67-71
29207067-8	2018	PKCbetaI and TGF-beta1 expression was increased in the PAF + HG + LPC group compared with the other groups (P<0.05); however, this effect was abolished in the presence of LY333531 (P<0.05).	ruboxistaurin	174-182	transforming growth factor beta 1	Homo sapiens	13-22
29207067-9	2018	Supernatant fibronectin and collagen IV levels were increased in the PAF + HG + LPC group compared with the others (P<0.05); this was reversed by treatment with LY333531 (P<0.05).	ruboxistaurin	164-172	fibronectin 1	Homo sapiens	12-23
28535942-6	2017	These effects were accompanied by upregulation of atrial protein kinase C subtypes beta and epsilon (PKCbeta and PKCepsilon), which was completely blocked by LY333531 and EAVSLKPT, antagonists of protein PKCbeta and PKCepsilon, respectively.	ruboxistaurin	158-166	protein kinase C, beta	Rattus norvegicus	101-108
28212798-11	2017	Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials.	ruboxistaurin	40-53	proline rich transmembrane protein 2	Homo sapiens	17-20
25808972-7	2015	Compared with non-diabetic, DM mice exhibited elevated atherosclerotic plaque formation, cholestoryl ester content and macrophage infiltration, as well as reduced IL-18BP expression in the aorta which was prevented with RBX treatment.	ruboxistaurin	220-223	interleukin 18 binding protein	Mus musculus	163-170
26585565-8	2016	GLP-1, added as an acute treatment in endothelial cells, had the capacity to induce the expression of Nrf2-detoxifying enzyme targets, to increase transcription levels of scavenger genes, to attenuate the expression of high glucose-induced PKA subunits, ER stress and also the apoptotic phenotype of HUVECs; these effects occured only when high glucose-induced PKCbeta overexpression was reduced by Ruboxistaurin.	ruboxistaurin	399-412	glucagon	Homo sapiens	0-5
26817709-0	2016	Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-beta1/Smad and GRAP pathways.	ruboxistaurin	0-13	transforming growth factor, beta 1	Rattus norvegicus	64-73
26817709-0	2016	Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-beta1/Smad and GRAP pathways.	ruboxistaurin	0-13	GRB2-related adaptor protein	Rattus norvegicus	83-87
26817709-1	2016	OBJECTIVE: To investigate whether ruboxistaurin (a selective PKC-beta inhibitor) mediates renoprotective effect via interference with TGF-beta1/Smad-GRAP cross-signalling.	ruboxistaurin	34-47	protein kinase C, beta	Rattus norvegicus	61-69
26817709-1	2016	OBJECTIVE: To investigate whether ruboxistaurin (a selective PKC-beta inhibitor) mediates renoprotective effect via interference with TGF-beta1/Smad-GRAP cross-signalling.	ruboxistaurin	34-47	transforming growth factor, beta 1	Rattus norvegicus	134-143
26817709-1	2016	OBJECTIVE: To investigate whether ruboxistaurin (a selective PKC-beta inhibitor) mediates renoprotective effect via interference with TGF-beta1/Smad-GRAP cross-signalling.	ruboxistaurin	34-47	GRB2-related adaptor protein	Rattus norvegicus	149-153
26817709-9	2016	A significant up-regulation of TGF-beta1, Smad2 and Smad3 mRNA expression was observed in diabetic rats, which was alleviated by administration of ruboxistaurin.	ruboxistaurin	147-160	transforming growth factor, beta 1	Rattus norvegicus	31-40
26817709-9	2016	A significant up-regulation of TGF-beta1, Smad2 and Smad3 mRNA expression was observed in diabetic rats, which was alleviated by administration of ruboxistaurin.	ruboxistaurin	147-160	SMAD family member 2	Rattus norvegicus	42-47
26817709-9	2016	A significant up-regulation of TGF-beta1, Smad2 and Smad3 mRNA expression was observed in diabetic rats, which was alleviated by administration of ruboxistaurin.	ruboxistaurin	147-160	SMAD family member 3	Rattus norvegicus	52-57
26817709-10	2016	Furthermore, immunoblotting showed a significant improvement in protein levels of TGF-beta1 (P < 0.01), Smad2/3 (P < 0.01) and p-Smad3 (P < 0.001) in diabetic rats treated with ruboxistaurin compared to untreated.	ruboxistaurin	186-199	transforming growth factor, beta 1	Rattus norvegicus	82-91
26817709-11	2016	Importantly, the reduction in GRAP protein expression in diabetic kidney was prevented by treatment with ruboxistaurin.	ruboxistaurin	105-118	GRB2-related adaptor protein	Rattus norvegicus	30-34
26817709-12	2016	CONCLUSION: These data suggest that the renoprotective effect of ruboxistaurin is possibly due to down-regulation of TGF-beta1/Smad pathway and normalization of GRAP protein expression.	ruboxistaurin	65-78	transforming growth factor, beta 1	Rattus norvegicus	117-126
26817709-12	2016	CONCLUSION: These data suggest that the renoprotective effect of ruboxistaurin is possibly due to down-regulation of TGF-beta1/Smad pathway and normalization of GRAP protein expression.	ruboxistaurin	65-78	GRB2-related adaptor protein	Rattus norvegicus	161-165
25849791-4	2015	Streptozotocin-induced diabetic rats were treated with the selective PKCbeta inhibitor ruboxistaurin (RBX, 1 mg/kg per day) for 4 weeks, starting from 1 week after diabetes induction, before inducing myocardial I/R achieved by occluding the left descending coronary artery followed by reperfusion.	ruboxistaurin	87-100	protein kinase C, beta	Rattus norvegicus	69-76
25849791-4	2015	Streptozotocin-induced diabetic rats were treated with the selective PKCbeta inhibitor ruboxistaurin (RBX, 1 mg/kg per day) for 4 weeks, starting from 1 week after diabetes induction, before inducing myocardial I/R achieved by occluding the left descending coronary artery followed by reperfusion.	ruboxistaurin	87-100	ring-box 1	Rattus norvegicus	102-108
25849791-8	2015	RBX significantly decreased post-ischaemic myocardial infarct size (35+-5% compared with 49+-3% in control, P<0.05) and attenuated cardiac dysfunction, and prevented the reduction in cardiac Cav-3 and enhanced phosphorylated/activated Akt (p-Akt) in diabetic rats (P<0.05).	ruboxistaurin	0-3	caveolin 3	Rattus norvegicus	194-199
25849791-8	2015	RBX significantly decreased post-ischaemic myocardial infarct size (35+-5% compared with 49+-3% in control, P<0.05) and attenuated cardiac dysfunction, and prevented the reduction in cardiac Cav-3 and enhanced phosphorylated/activated Akt (p-Akt) in diabetic rats (P<0.05).	ruboxistaurin	0-3	AKT serine/threonine kinase 1	Rattus norvegicus	238-241
25849791-8	2015	RBX significantly decreased post-ischaemic myocardial infarct size (35+-5% compared with 49+-3% in control, P<0.05) and attenuated cardiac dysfunction, and prevented the reduction in cardiac Cav-3 and enhanced phosphorylated/activated Akt (p-Akt) in diabetic rats (P<0.05).	ruboxistaurin	0-3	AKT serine/threonine kinase 1	Rattus norvegicus	245-248
26501476-6	2016	Although initial studies have indicated that the treatment of diabetic patients with ruboxistaurin, a specific inhibitor of PKCbeta, may reduce visual loss in patients with diabetic retinopathy, the overall benefit seems to be small.	ruboxistaurin	85-98	protein kinase C beta	Homo sapiens	124-131
26657401-8	2015	Besides Ro 31-8220, 7 additional BIMs, including the PKC inhibitor LY 333531, inhibited OCT1 activity, whereas 4 other BIMs were without effect.	ruboxistaurin	67-76	solute carrier family 22 member 1	Homo sapiens	88-92
25815500-2	2015	METHODS: A549 cells were cultured in vitro and randomly divided into three groups: control, hyperoxia and PKCbeta inhibitor LY333531 treatment.	ruboxistaurin	124-132	protein kinase C beta	Homo sapiens	106-113
25789114-9	2015	Moreover, the review provides insights on the effectiveness of available compounds (i.e., ruboxistaurin, sildenafil, endothelin receptor antagonists, NO donors) in restoring endothelial insulin signalling.	ruboxistaurin	90-103	insulin	Homo sapiens	186-193
25815500-4	2015	The LY333531 group was treated with PKCbeta inhibitor LY333531 of 10 micromol/L for 24 hours before hyperoxia induction.	ruboxistaurin	4-12	protein kinase C beta	Homo sapiens	36-43
25815500-4	2015	The LY333531 group was treated with PKCbeta inhibitor LY333531 of 10 micromol/L for 24 hours before hyperoxia induction.	ruboxistaurin	54-62	protein kinase C beta	Homo sapiens	36-43
25815500-12	2015	PKCbeta inhibitor LY333531 can partially disrupt these changes and thus alleviate the hyperoxia-induced alveolar epithelial cell injury.	ruboxistaurin	18-26	protein kinase C beta	Homo sapiens	0-7
24722289-5	2014	Ruboxistaurin (PKCbeta inhibitor) or normal saline was administered before ischemia.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	15-22
24930012-9	2014	In addition, LY333531 markedly restrained p66shc activation, mitochondrial translocation, and binding to cytochrome-c.	ruboxistaurin	13-21	src homology 2 domain-containing transforming protein C1	Mus musculus	42-48
24998254-11	2014	In TAC-mice, 3-methyladenine administration also ameliorated heart hypertrophy, fibrosis and dysfunction, while LY333531 administration inhibited ERK phosphorylation and autophagy in heart.	ruboxistaurin	112-120	mitogen-activated protein kinase 1	Mus musculus	146-149
24694591-4	2014	Here, we showed that, although the caveolin-1 protein level had no significant change, the PKC-beta-specific inhibitor LY-333531 blocked caveolin-1 Y14 phosphorylation in high glucose (HG)-treated MCs and in the renal cortex of diabetic rats.	ruboxistaurin	119-128	protein kinase C, beta	Rattus norvegicus	91-99
24694591-4	2014	Here, we showed that, although the caveolin-1 protein level had no significant change, the PKC-beta-specific inhibitor LY-333531 blocked caveolin-1 Y14 phosphorylation in high glucose (HG)-treated MCs and in the renal cortex of diabetic rats.	ruboxistaurin	119-128	caveolin 1	Rattus norvegicus	137-147
24722289-9	2014	Ruboxistaurin significantly attenuated gut damage and decreased the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).	ruboxistaurin	0-13	tumor necrosis factor	Homo sapiens	84-111
24722289-9	2014	Ruboxistaurin significantly attenuated gut damage and decreased the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).	ruboxistaurin	0-13	tumor necrosis factor	Homo sapiens	113-122
24722289-9	2014	Ruboxistaurin significantly attenuated gut damage and decreased the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).	ruboxistaurin	0-13	interleukin 6	Homo sapiens	128-141
24722289-9	2014	Ruboxistaurin significantly attenuated gut damage and decreased the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).	ruboxistaurin	0-13	interleukin 6	Homo sapiens	143-147
24722289-12	2014	Phorbol 12-myristate 13-acetate (PMA), which stimulates PKCs, induced p66(Shc) phosphorylation and this was inhibited by ruboxistaurin and PKCbeta2 siRNA.	ruboxistaurin	121-134	DNA polymerase delta 3, accessory subunit	Homo sapiens	70-73
24722289-12	2014	Phorbol 12-myristate 13-acetate (PMA), which stimulates PKCs, induced p66(Shc) phosphorylation and this was inhibited by ruboxistaurin and PKCbeta2 siRNA.	ruboxistaurin	121-134	SHC adaptor protein 1	Homo sapiens	74-77
24722289-13	2014	Ruboxistaurin attenuated gut oxidative stress after I/R by suppressing the decreased expression of manganese superoxide dismutase (MnSOD), the exhaustion of the glutathione (GSH) system, and the overproduction of malondialdehyde (MDA).	ruboxistaurin	0-13	superoxide dismutase 2	Homo sapiens	99-129
24722289-13	2014	Ruboxistaurin attenuated gut oxidative stress after I/R by suppressing the decreased expression of manganese superoxide dismutase (MnSOD), the exhaustion of the glutathione (GSH) system, and the overproduction of malondialdehyde (MDA).	ruboxistaurin	0-13	superoxide dismutase 2	Homo sapiens	131-136
24008236-5	2013	Protein kinase C (PKC) pathways were investigated by pretreatment with PKC-beta inhibitor ruboxistaurin or pan-PKC inhibitor GF109203X.	ruboxistaurin	90-103	protein kinase C beta	Homo sapiens	18-21
24002353-8	2013	Furthermore, treatment of rats with LY333 not only significantly increased the capillary density of ischemic myocardium, but also significantly elevated the levels of p-Akt and p-eNOS expression.	ruboxistaurin	36-41	AKT serine/threonine kinase 1	Rattus norvegicus	169-172
24002353-9	2013	We also observed a significant increase of VEGF expression in myocardium measured by immunostaining in MI and LY333 groups compared to sham group.	ruboxistaurin	110-115	vascular endothelial growth factor A	Rattus norvegicus	43-47
23474486-9	2013	LY333531 suppressed the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigated the augmentation of O2(-), nitrotyrosine, Cav-1, and iNOS expression.	ruboxistaurin	0-8	caveolin 3	Rattus norvegicus	63-68
23474486-9	2013	LY333531 suppressed the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigated the augmentation of O2(-), nitrotyrosine, Cav-1, and iNOS expression.	ruboxistaurin	0-8	AKT serine/threonine kinase 1	Rattus norvegicus	89-92
23474486-9	2013	LY333531 suppressed the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigated the augmentation of O2(-), nitrotyrosine, Cav-1, and iNOS expression.	ruboxistaurin	0-8	nitric oxide synthase 3	Rattus norvegicus	100-104
23474486-9	2013	LY333531 suppressed the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigated the augmentation of O2(-), nitrotyrosine, Cav-1, and iNOS expression.	ruboxistaurin	0-8	caveolin 1	Rattus norvegicus	166-171
23474486-9	2013	LY333531 suppressed the decreased expression of myocardial NO, Cav-3, phosphorylated (p)-Akt, and p-eNOS and also mitigated the augmentation of O2(-), nitrotyrosine, Cav-1, and iNOS expression.	ruboxistaurin	0-8	nitric oxide synthase 2	Rattus norvegicus	177-181
23514610-6	2013	LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001).	ruboxistaurin	0-8	proline rich transmembrane protein 2	Homo sapiens	80-83
24497733-5	2013	Studies show that oral administration of PKCbeta inhibitor Ruboxistaurin (LY333531), decreases vessel permeability and improves retinal condition.	ruboxistaurin	59-72	protein kinase C beta	Homo sapiens	41-48
24497733-5	2013	Studies show that oral administration of PKCbeta inhibitor Ruboxistaurin (LY333531), decreases vessel permeability and improves retinal condition.	ruboxistaurin	74-82	protein kinase C beta	Homo sapiens	41-48
22569400-7	2012	Finally, we show that PTPN22 can be effectively down-regulated by the PKC inhibitors ruboxistaurin and sotrastaurin, resulting in enhanced killing of CLL cells exposed to proapoptotic BCR stimuli.	ruboxistaurin	85-98	protein tyrosine phosphatase non-receptor type 22	Homo sapiens	22-28
21892921-0	2012	PKCbeta inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes.	ruboxistaurin	24-37	protein kinase C, beta	Rattus norvegicus	0-7
21892921-4	2012	Control or streptozotocin-induced diabetic rats were treated with the selective PKCbeta inhibitor RBX (ruboxistaurin; 1 mg/kg of body weight per day) or the antioxidant NAC (N-acetylcysteine) for 4 weeks.	ruboxistaurin	98-101	protein kinase C, beta	Rattus norvegicus	80-87
21892921-9	2012	RBX normalized these changes with concomitant inhibition of PKCbeta2 activation and prevention of NADPH oxidase subunit p67phox membrane translocation and p22phox overexpression.	ruboxistaurin	0-3	cytochrome b-245 alpha chain	Rattus norvegicus	155-162
21998327-0	2011	Inhibition of PKCalpha/beta with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury.	ruboxistaurin	33-46	protein kinase C alpha	Homo sapiens	14-22
21998327-3	2011	Pharmacological inhibition of PKCalpha/beta with Ro-32-0432, Ro-31-8220 or ruboxistaurin (LY333531) similarly enhances cardiac function and antagonizes heart failure in multiple models of disease in both mice and rats.	ruboxistaurin	75-88	protein kinase C, alpha	Mus musculus	30-38
21998327-3	2011	Pharmacological inhibition of PKCalpha/beta with Ro-32-0432, Ro-31-8220 or ruboxistaurin (LY333531) similarly enhances cardiac function and antagonizes heart failure in multiple models of disease in both mice and rats.	ruboxistaurin	90-98	protein kinase C, alpha	Mus musculus	30-38
21998327-8	2011	CONCLUSIONS: These results provide additional evidence in a large animal model of disease that PKCalpha/beta inhibition (with ruboxistaurin) represents a tenable and novel therapeutic approach for treating human heart failure.	ruboxistaurin	126-139	protein kinase C alpha	Homo sapiens	95-103
21864610-7	2011	Furthermore, pre-incubation of the cells with the selective PKCalpha/beta inhibitor Go6976 abolished the downregulation effect of phorbol ester on uptake and phosphorylation, whereas the selective PKCbeta inhibitors (PKCbeta inhibitor or LY333531) prevented the phosphorylation without affecting glycine uptake, defining a specific role of classical PKC on GlyT1 uptake and phosphorylation.	ruboxistaurin	238-246	protein kinase C alpha	Homo sapiens	60-73
21864610-7	2011	Furthermore, pre-incubation of the cells with the selective PKCalpha/beta inhibitor Go6976 abolished the downregulation effect of phorbol ester on uptake and phosphorylation, whereas the selective PKCbeta inhibitors (PKCbeta inhibitor or LY333531) prevented the phosphorylation without affecting glycine uptake, defining a specific role of classical PKC on GlyT1 uptake and phosphorylation.	ruboxistaurin	238-246	protein kinase C alpha	Homo sapiens	60-63
22204135-3	2011	Thus the effect of the selective PKC-beta inhibitor (LY333531) on AGEs-induced HUVEC apoptosis and proliferation was investigated.	ruboxistaurin	53-61	protein kinase C beta	Homo sapiens	33-41
22204135-9	2011	Moreover, LY333531 reduced the ratio of Bcl-2/Bax.	ruboxistaurin	10-18	BCL2 apoptosis regulator	Homo sapiens	40-45
22204135-9	2011	Moreover, LY333531 reduced the ratio of Bcl-2/Bax.	ruboxistaurin	10-18	BCL2 associated X, apoptosis regulator	Homo sapiens	46-49
22204135-10	2011	The results indicate that the selective PKC-beta inhibitor, LY333531, can further prompt AGEs-induced endothelial cells apoptosis.	ruboxistaurin	60-68	protein kinase C beta	Homo sapiens	40-48
23316263-6	2011	Treating diabetic mice with the PKC beta inhibitor ruboxistaurin for 5 weeks lowered ADM mRNA levels and ADM-like immunoreactivity and preserved retinal function as assessed by electroretinography.	ruboxistaurin	51-64	protein kinase C, beta	Mus musculus	32-40
22520069-6	2012	A new promising therapy for diabetic retinopathy is undergoing Phase III trials, in which they proposed to target PKC betaII isomer using Ruboxistaurin by oral administration.	ruboxistaurin	138-151	proline rich transmembrane protein 2	Homo sapiens	114-117
22586590-7	2012	Treatment with ruboxistaurin (a PKCbeta inhibitor) or with GW501516 (a peroxisome proliferator-activated receptor delta activator) reduced atrogin-1 expression and restored BK channel-mediated coronary vasodilation in diabetic mice.	ruboxistaurin	15-28	protein kinase C, beta	Mus musculus	32-39
22586590-7	2012	Treatment with ruboxistaurin (a PKCbeta inhibitor) or with GW501516 (a peroxisome proliferator-activated receptor delta activator) reduced atrogin-1 expression and restored BK channel-mediated coronary vasodilation in diabetic mice.	ruboxistaurin	15-28	F-box protein 32	Homo sapiens	139-148
21989030-6	2012	Furthermore, the generation of reactive oxygen species, production of nitric oxide, and expression of inducible nitric oxide synthase induced by advanced glycation end products were inhibited by PKCbeta inhibitor LY-333531 or a PKA agonist in rat glomerular microvascular endothelial cells.	ruboxistaurin	213-222	protein kinase C, beta	Rattus norvegicus	195-202
21228767-5	2011	Treatment with the protein kinase C-beta inhibitor, ruboxistaurin, enhanced insulin actions and elevated IRS1 expression.	ruboxistaurin	52-65	insulin receptor substrate 1	Rattus norvegicus	105-109
21241763-7	2011	In addition, DEX-stimulated GDNF release was also blocked by the universal PKC inhibitor Ro-318220 and PKCalpha/beta inhibitor Go 6976, but not by PKCdelta inhibitor rottlerin and PKCbeta inhibitor LY333531.	ruboxistaurin	198-206	glial cell derived neurotrophic factor	Rattus norvegicus	28-32
20939796-9	2011	Ruboxistaurin, an orally PKCbeta inhibitor has demonstrated in vitro and in vivo benefits in dimisnish cell and blood flow alterations related to hyperglycemia and has a potential use as a therapy for DR and DME.	ruboxistaurin	0-13	protein kinase C beta	Homo sapiens	25-32
20939796-11	2011	The ability of Ruboxistaurin in reducing visual loss in patients with DR has been demonstrated in the PKC DRS2 trial and DME seems to respond to Ruboxistaurin with both anatomic and functional benefits.	ruboxistaurin	15-28	protein kinase C beta	Homo sapiens	102-105
20939796-11	2011	The ability of Ruboxistaurin in reducing visual loss in patients with DR has been demonstrated in the PKC DRS2 trial and DME seems to respond to Ruboxistaurin with both anatomic and functional benefits.	ruboxistaurin	15-28	dishevelled segment polarity protein 1	Homo sapiens	106-110