PMID-sentid	Pub_year	Sent_text	comp_official_name	comp_offset	protein_name	organism	prot_offset
24832603-9	2014	Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice.	Estradiol	117-126	TSC complex subunit 2	Mus musculus	91-95
25155956-5	2014	The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2 +- mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2 +- :Atg7(CKO) double mutants.	Sirolimus	19-28	TSC complex subunit 2	Mus musculus	87-91
24976129-4	2014	Synergistic exposure of CEES and LPS provoked significant increase in phosphorylation of MAPKs, Akt, tuberin, that down regulate OGG1 expression and 8-OHdG accumulations.	cees	24-28	TSC complex subunit 2	Mus musculus	101-108
24976129-4	2014	Synergistic exposure of CEES and LPS provoked significant increase in phosphorylation of MAPKs, Akt, tuberin, that down regulate OGG1 expression and 8-OHdG accumulations.	8-ohdg	149-155	TSC complex subunit 2	Mus musculus	101-108
24976129-6	2014	In addition, the N-acetylcysteine inhibited ROS/RNS generation, elevation of antioxidants level, expression of ERK1/2, Akt, tuberin phosphorylation, resulted in deceased 8-OHdG accumulation and upregulation of OGG1 protein expression suggesting no involvement of Akt and ERK1/2MAPK pathways after CEES and LPS challenge.	Acetylcysteine	17-33	TSC complex subunit 2	Mus musculus	124-131
24976129-7	2014	Collectively, our results indicate that exposure of CEES and LPS induces oxidative stress and the activation of tuberin, and 8-OHdG accumulation via upstream signaling pathways including Akt and ERK1/2MAPK pathway in macrophages but not the down regulation of OGG1.	cees	52-56	TSC complex subunit 2	Mus musculus	112-119
25613864-0	2015	Prolonging the survival of Tsc2 conditional knockout mice by glutamine supplementation.	Glutamine	61-70	TSC complex subunit 2	Mus musculus	27-31
25613864-1	2015	The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity.	Sirolimus	229-238	TSC complex subunit 2	Mus musculus	153-157
25613864-1	2015	The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity.	Sirolimus	229-238	TSC complex subunit 2	Mus musculus	159-166
25613864-9	2015	When administered orally to TSC2 knockout mice, glutamine reduced S6 phosphorylation in the brain and significantly prolonged their lifespan.	Glutamine	48-57	TSC complex subunit 2	Mus musculus	28-32
24632604-0	2015	Renal tumours in a Tsc2(+/-) mouse model do not show feedback inhibition of Akt and are effectively prevented by rapamycin.	Sirolimus	113-122	TSC complex subunit 2	Mus musculus	19-23
24632604-10	2015	In conclusion, in contrast to previous studies, we found that Akt signalling is not inhibited in Tsc-associated renal lesions and that by partially inhibiting the Akt/mTOR pathway, rapamycin is highly effective in preventing Tsc-associated tumours.	Sirolimus	181-190	TSC complex subunit 2	Mus musculus	225-228
24832603-4	2014	Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells.	Pentosephosphates	65-82	TSC complex subunit 2	Mus musculus	104-108
24832603-10	2014	Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells.	6-Aminonicotinamide	96-115	TSC complex subunit 2	Mus musculus	179-183
23081885-4	2014	Then, we show that Tsc2 shRNA knockdown (KD) in mouse neural progenitor cells (mNPCs) in vitro results in enhanced mTORC1 (phospho-S6, phospho-4E-BP1) and mTORC2 (phospho-Akt and phospho-NDRG1) signaling, as well as a doubling of cell size that is rescued by rapamycin, an mTORC1 inhibitor.	Sirolimus	259-268	TSC complex subunit 2	Mus musculus	19-23
23604129-5	2014	However, murine embryonic fibroblasts (MEFs) lacking TSC2 were highly resistant to ceramide-induced death.	Ceramides	83-91	TSC complex subunit 2	Mus musculus	53-57
24564913-7	2014	In Tsc2 heterozygous (+/-) mice, immune system-related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly changed in both tissues.	Glycolipids	104-114	TSC complex subunit 2	Mus musculus	3-7
23081885-5	2014	Tsc2 KD in vivo in the fetal mouse brain by in utero electroporation causes disorganized cortical lamination and increased cell volume that is prevented with rapamycin.	Sirolimus	158-167	TSC complex subunit 2	Mus musculus	0-4
23517912-5	2013	To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells.	fisetin	140-147	TSC complex subunit 2	Mus musculus	156-160
23947572-6	2013	Simvastatin, but not atorvastatin, showed a concentration-dependent (0.5-10 muM) inhibitory effect on mouse TSC2-null and human LAM-derived cell growth.	Simvastatin	0-11	TSC complex subunit 2	Mus musculus	108-112
23810968-14	2013	Activation of mTOR by insulin or inhibition of endogenous TSC2 levels by siRNA obviously delayed PAB-induced senescence.	pseudolaric acid B	97-100	TSC complex subunit 2	Mus musculus	58-62
23884148-7	2013	We demonstrate that mTOR signaling is activated in the renal collecting ducts of lithium-treated mice; lithium increased the phosphorylation of rS6 (Ser240/Ser244), p-TSC2 (Thr1462), and p-mTOR (Ser2448).	Lithium	81-88	TSC complex subunit 2	Mus musculus	167-171
23884148-7	2013	We demonstrate that mTOR signaling is activated in the renal collecting ducts of lithium-treated mice; lithium increased the phosphorylation of rS6 (Ser240/Ser244), p-TSC2 (Thr1462), and p-mTOR (Ser2448).	Lithium	103-110	TSC complex subunit 2	Mus musculus	167-171
23901139-7	2013	Preventing phosphatidylcholine from binding to PC-TP disrupted interactions of PC-TP with THEM2 and TSC2, and disruption of the PC-TP-THEM2 complex was associated with increased activation of both IRS2 and mTORC1.	Phosphatidylcholines	11-30	TSC complex subunit 2	Mus musculus	100-104
23035046-5	2012	TSC2-null lesions and alveolar destruction were differentially inhibited by the macrolide antibiotic rapamycin (which inhibits TSC2-null lesion growth by a cytostatic mechanism) and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, simvastatin (which inhibits growth of TSC2-null lesions by a predominantly proapoptotic mechanism).	Macrolides	80-89	TSC complex subunit 2	Mus musculus	0-4
23228442-2	2013	Recent studies suggest that metformin attenuates mTORC1 signalling by the activation of 5" adenosine monophosphate-activated protein kinase (AMPK) in the presence or absence of a functional hamartin/tuberin (TSC1/TSC2) complex.	Metformin	28-37	TSC complex subunit 2	Mus musculus	213-217
23696882-8	2013	Knockdown of TSC2, a negative regulator of mTORC1, caused activation of mTORC1 and enhanced Cd induction of the IRE1-JNK pathway and apoptosis without affecting other UPR branches.	Cadmium	92-94	TSC complex subunit 2	Mus musculus	13-17
23035046-5	2012	TSC2-null lesions and alveolar destruction were differentially inhibited by the macrolide antibiotic rapamycin (which inhibits TSC2-null lesion growth by a cytostatic mechanism) and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, simvastatin (which inhibits growth of TSC2-null lesions by a predominantly proapoptotic mechanism).	Simvastatin	243-254	TSC complex subunit 2	Mus musculus	0-4
23035046-7	2012	The combination of rapamycin and simvastatin prevented both growth of TSC2-null lesions and lung destruction by inhibiting MMP-2, MMP-3, and MMP-9.	Sirolimus	19-28	TSC complex subunit 2	Mus musculus	70-74
23035046-7	2012	The combination of rapamycin and simvastatin prevented both growth of TSC2-null lesions and lung destruction by inhibiting MMP-2, MMP-3, and MMP-9.	Simvastatin	33-44	TSC complex subunit 2	Mus musculus	70-74
21802234-5	2012	One Tsc2(+/-) mouse was treated with rapamycin for two months after the initial scan.	Sirolimus	37-46	TSC complex subunit 2	Mus musculus	4-8
21802234-10	2012	By MRI, these lesions demonstrated significant growth in the 9 untreated Tsc1(+/-) and Tsc2(+/-) mice but shrinkage in the rapamycin treated Tsc2(+/-) mouse.	Sirolimus	123-132	TSC complex subunit 2	Mus musculus	141-145
22184110-8	2012	Moreover, inhibition of deregulated TORC1 in TSC2-null mouse embryonic fibroblasts or in 293 cells by down-regulation of raptor decreased the levels of the transcription factor Hif1alpha and blocked PTEN expression, resulting in enhanced phosphorylation of Akt at Thr-308 and Ser-473.	Threonine	264-267	TSC complex subunit 2	Mus musculus	45-49
22184110-8	2012	Moreover, inhibition of deregulated TORC1 in TSC2-null mouse embryonic fibroblasts or in 293 cells by down-regulation of raptor decreased the levels of the transcription factor Hif1alpha and blocked PTEN expression, resulting in enhanced phosphorylation of Akt at Thr-308 and Ser-473.	Serine	276-279	TSC complex subunit 2	Mus musculus	45-49
21062901-7	2011	The differences between Tsc1(GFAP1)CKO and Tsc2(GFAP1)CKO mice were correlated with higher levels of mammalian target of rapamycin (mTOR) activation in Tsc2(GFAP1)CKO mice and were reversed by the mTOR inhibitor, rapamycin.	Sirolimus	121-130	TSC complex subunit 2	Mus musculus	43-47
22018000-3	2011	In particular, cells with constitutive mTORC1 activity secondary to the loss of TSC1/TSC2 function are prone to undergo apoptosis upon glucose withdrawal in vitro, but this concept has not been tested in vivo.	Glucose	135-142	TSC complex subunit 2	Mus musculus	85-89
22018000-9	2011	Alternative energy substrates such as ketone bodies and monounsaturated oleic acid supported the growth of the Tsc2-/- cells in vitro, whereas saturated palmitic acid was toxic.	Ketones	38-44	TSC complex subunit 2	Mus musculus	111-115
22018000-9	2011	Alternative energy substrates such as ketone bodies and monounsaturated oleic acid supported the growth of the Tsc2-/- cells in vitro, whereas saturated palmitic acid was toxic.	monounsaturated oleic acid	56-82	TSC complex subunit 2	Mus musculus	111-115
21418186-0	2011	Doxycycline inhibits matrix metalloproteinase-2 secretion from TSC2-null mouse embryonic fibroblasts and lymphangioleiomyomatosis cells.	Doxycycline	0-11	TSC complex subunit 2	Mus musculus	63-67
20160076-0	2010	ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS.	Reactive Oxygen Species	71-74	TSC complex subunit 2	Mus musculus	15-19
20656472-10	2010	In contrast, transfection of Tsc2(+/-) cells with DN-S6K abolished p70S6K phosphorylation and increased OGG1 expression, a response enhanced by rapamycin.	Sirolimus	144-153	TSC complex subunit 2	Mus musculus	29-33
20656472-11	2010	Treatment of Tsc2(+/-) mice with rapamycin resulted in activation of AMPK, downregulation of phospho-p70S6K and enhanced OGG1 expression.	Sirolimus	33-42	TSC complex subunit 2	Mus musculus	13-17
20656472-2	2010	In early clinical trials, tuberous sclerosis complex (TSC)-related kidney tumours were found to regress following rapamycin treatment.	Sirolimus	114-123	TSC complex subunit 2	Mus musculus	54-57
20656472-4	2010	Treatment of HK2 cells, mouse Tsc-deficient cells and human VHL-deficient cells (786-O) with rapamycin resulted in decrease in p70S6K phosphorylation at Thr(389), and increase in the expression of NF-YA and OGG1 proteins.	Sirolimus	93-102	TSC complex subunit 2	Mus musculus	30-33
20656472-4	2010	Treatment of HK2 cells, mouse Tsc-deficient cells and human VHL-deficient cells (786-O) with rapamycin resulted in decrease in p70S6K phosphorylation at Thr(389), and increase in the expression of NF-YA and OGG1 proteins.	Threonine	153-156	TSC complex subunit 2	Mus musculus	30-33
20159776-8	2010	In response to artery injury using a carotid artery ligation model, Tsc2(+/-) mice significantly increased neointima formation compared with the control mice, and the neointima formation was inhibited by treatment with rapamycin.	Sirolimus	219-228	TSC complex subunit 2	Mus musculus	68-72
20160076-7	2010	Our results identify a cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy, identifying an integration node for the cellular damage response with key pathways involved in metabolism, protein synthesis, and cell survival.	Reactive Oxygen Species	47-50	TSC complex subunit 2	Mus musculus	77-81
19602587-5	2009	In this study, we show that both phosphatidylinositol 3-kinase-dependent and phosphatidylinositol 3-kinase-independent mTORC2 substrates are affected by loss of the TSC1-TSC2 complex in cell culture models and kidney tumors from both Tsc2(+/-) mice (adenoma) and TSC patients (angiomyolipoma).	Phosphatidylinositols	33-53	TSC complex subunit 2	Mus musculus	234-238
19738049-4	2009	We observed the same characteristics in wild-type primary cultures of CGNPs in which TSC1 and/or TSC2 were knocked down, and in mouse medulloblastomas induced by ectopic Shh pathway activation.	cgnps	70-75	TSC complex subunit 2	Mus musculus	97-101
20146790-0	2010	Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors.	Sirolimus	20-29	TSC complex subunit 2	Mus musculus	54-58
20146790-2	2010	Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment.	Sirolimus	0-9	TSC complex subunit 2	Mus musculus	86-89
20146790-9	2010	When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks.	Sirolimus	5-14	TSC complex subunit 2	Mus musculus	53-57
19420259-5	2009	In Tsc2-deficient neurons, the expression of stress markers such as CHOP and HO-1 is increased, and this increase is completely reversed by the mTOR inhibitor rapamycin both in vitro and in vivo.	Sirolimus	159-168	TSC complex subunit 2	Mus musculus	3-7
19584242-3	2009	We tested atorvastatin as a therapy for (a) ethylnitrosourea (ENU)-enhanced renal cystadenoma and (b) spontaneous liver hemangioma in 129Sv/Jae Tsc2(+/-) mice.	Atorvastatin	10-22	TSC complex subunit 2	Mus musculus	144-148
19539245-6	2009	Investigation of this hypothesis in a TSC cell model revealed that mTOR suppression with an mTOR inhibitor, rapamycin (sirolimus), led to up-regulation of ERK/MAPK signaling in mouse Tsc2 knockout cells and that this augmented signaling was attenuated by concurrent administration of a MEK1/2 inhibitor, PD98059.	Sirolimus	108-117	TSC complex subunit 2	Mus musculus	183-187
19539245-6	2009	Investigation of this hypothesis in a TSC cell model revealed that mTOR suppression with an mTOR inhibitor, rapamycin (sirolimus), led to up-regulation of ERK/MAPK signaling in mouse Tsc2 knockout cells and that this augmented signaling was attenuated by concurrent administration of a MEK1/2 inhibitor, PD98059.	Sirolimus	119-128	TSC complex subunit 2	Mus musculus	183-187
19539245-6	2009	Investigation of this hypothesis in a TSC cell model revealed that mTOR suppression with an mTOR inhibitor, rapamycin (sirolimus), led to up-regulation of ERK/MAPK signaling in mouse Tsc2 knockout cells and that this augmented signaling was attenuated by concurrent administration of a MEK1/2 inhibitor, PD98059.	2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	304-311	TSC complex subunit 2	Mus musculus	183-187
19143643-8	2009	Recent studies in mouse models carrying heterozygous Tsc2 mutations demonstrated improvement in memory and learning deficits following treatment with rapamycin.	Sirolimus	150-159	TSC complex subunit 2	Mus musculus	53-57
19368729-6	2009	RESULTS: Here, we examine the efficacy of a prolonged maintenance dose of rapamycin in Tsc2+/- mice with TSC-related kidney tumors.	Sirolimus	74-83	TSC complex subunit 2	Mus musculus	87-91
19368729-9	2009	We observed a 94.5% reduction in kidney tumor burden in Tsc2+/- mice treated (part one) daily with rapamycin (8 mg/kg) at 6 months <or= age < 7 months, (part 2) weekly with rapamycin (16 mg/kg) at 7 months <or= age < 12 months, and (part 3) daily with rapamycin (8 mg/kg) at 12 months <or= age < 13 months; but we did not observe any improvement with combination IFN-g plus rapamycin in this study.	Sirolimus	99-108	TSC complex subunit 2	Mus musculus	56-60
19202070-3	2009	We report here that 17-beta-estradiol (E(2)) causes a 3- to 5-fold increase in pulmonary metastases in male and female mice, respectively, and a striking increase in circulating tumor cells in mice bearing tuberin-null xenograft tumors.	Estradiol	20-37	TSC complex subunit 2	Mus musculus	206-213
19202070-6	2009	Finally, using a bioluminescence approach, we found that E(2) enhances the survival and lung colonization of intravenously injected tuberin-null cells by 3-fold, which is blocked by treatment with CI-1040.	morin	197-199	TSC complex subunit 2	Mus musculus	132-139
18664580-5	2008	Tumors from Tsc2(+/-)E mu-Myc mice underwent rapid apoptosis upon blockade of mTORC1 by rapamycin.	Sirolimus	88-97	TSC complex subunit 2	Mus musculus	12-16
18587048-10	2008	The reduction of beta cell mass in betaTsc2(-/-) mice by inhibition of the mTOR/Raptor (TORC1) complex with rapamycin treatment suggests that TORC1 mediates proliferative and growth signals induced by deletion of Tsc2 in beta cells.	Sirolimus	108-117	TSC complex subunit 2	Mus musculus	39-43
18587048-11	2008	These studies uncover a critical role for the Tsc2/mTOR pathway in regulation of beta cell mass and carbohydrate metabolism in vivo.	Carbohydrates	100-112	TSC complex subunit 2	Mus musculus	46-50
17989114-5	2008	Mouse embryonic fibroblasts deficient in tuberin (TSC2(-/-) and TSC2(+/-)) also had markedly decreased OGG1 mRNA and protein expression, as well as undetectable OGG1 activity accompanied by accumulation of 8-oxodG.	8-ohdg	206-213	TSC complex subunit 2	Mus musculus	41-48
18354181-3	2008	In human and mouse mast cells, stimulation via FcepsilonRI or Kit resulted in a marked PI3K-dependent activation of the mTORC1 pathway, as revealed by the wortmannin-sensitive sequential phosphorylation of tuberin, mTOR, p70S6 kinase (p70S6K), and 4E-BP1.	Wortmannin	155-165	TSC complex subunit 2	Mus musculus	206-213
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	geranylgeranyl pyrophosphate	48-75	TSC complex subunit 2	Mus musculus	140-144
17942919-0	2007	Selective inhibition of growth of tuberous sclerosis complex 2 null cells by atorvastatin is associated with impaired Rheb and Rho GTPase function and reduced mTOR/S6 kinase activity.	Atorvastatin	77-89	TSC complex subunit 2	Mus musculus	34-62
17942919-4	2007	We show that atorvastatin selectively inhibits the proliferation of Tsc2-/- mouse embryo fibroblasts and ELT-3 smooth muscle cells in response to serum and estrogen, and under serum-free conditions.	Atorvastatin	13-25	TSC complex subunit 2	Mus musculus	68-72
18089792-5	2007	Deguelin inhibited survivin expression in tuberous sclerosis complex 2 (TSC2) wild-type mouse embryonic fibroblasts (MEF) but not in TSC2-knockout MEFs in which mammalian target of rapamycin (mTOR) is constitutively active.	deguelin	0-8	TSC complex subunit 2	Mus musculus	42-70
18089792-5	2007	Deguelin inhibited survivin expression in tuberous sclerosis complex 2 (TSC2) wild-type mouse embryonic fibroblasts (MEF) but not in TSC2-knockout MEFs in which mammalian target of rapamycin (mTOR) is constitutively active.	deguelin	0-8	TSC complex subunit 2	Mus musculus	72-76
17986349-12	2007	Treatment with rapamycin was more effective in reducing tumor growth and improving survival in nude mice bearing Tsc2-/- tumors and also resulted in higher rapamycin levels in blood, brain, and kidney tissue than treatment with an equal milligram dose of CCI-779.	Sirolimus	15-24	TSC complex subunit 2	Mus musculus	113-117
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	geranylgeranyl pyrophosphate	77-81	TSC complex subunit 2	Mus musculus	140-144
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	Terpenes	4-15	TSC complex subunit 2	Mus musculus	140-144
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	Atorvastatin	105-117	TSC complex subunit 2	Mus musculus	140-144
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	Terpenes	4-15	TSC complex subunit 2	Mus musculus	330-334
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	farnesyl pyrophosphate	16-37	TSC complex subunit 2	Mus musculus	140-144
17942919-8	2007	Atorvastatin, but not rapamycin, attenuated the increased levels of activated RhoA in Tsc2-/- cells, and this was reversed by GGPP.	Atorvastatin	0-12	TSC complex subunit 2	Mus musculus	86-90
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	farnesyl pyrophosphate	16-37	TSC complex subunit 2	Mus musculus	330-334
17942919-9	2007	These results suggest that atorvastatin may inhibit both rapamycin-sensitive and rapamycin-insensitive mechanisms of tuberin-null cell growth, likely via Rheb and Rho inhibition, respectively.	Atorvastatin	27-39	TSC complex subunit 2	Mus musculus	117-124
17942919-5	2007	The isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibition of Tsc2-/- cell growth, suggesting that atorvastatin dually targets a farnesylated protein, such as Rheb, and a geranylgeranylated protein, such as Rho, both of which have elevated activity in Tsc2-/- cells.	farnesyl pyrophosphate	39-42	TSC complex subunit 2	Mus musculus	140-144
17460049-3	2007	Akt1 deficiency delayed tumor growth and reduced lung metastases, correlating with a reduction in phosphorylation of the Akt1 target, tuberous sclerosis 2 (TSC2) at Ser-939.	Serine	165-168	TSC complex subunit 2	Mus musculus	134-154
17460049-3	2007	Akt1 deficiency delayed tumor growth and reduced lung metastases, correlating with a reduction in phosphorylation of the Akt1 target, tuberous sclerosis 2 (TSC2) at Ser-939.	Serine	165-168	TSC complex subunit 2	Mus musculus	156-160
17290308-4	2007	This was a direct effect of mTOR activation, since rapamycin restored PDGFR expression and PDGF-sensitive Akt activation in Tsc1-/- and Tsc2-/- cells.	Sirolimus	51-60	TSC complex subunit 2	Mus musculus	136-140
32796887-7	2020	Finally, Tsc2 CKO mice manifested increased susceptibility to dextran sulfate sodium-induced colitis.	Dextran Sulfate	62-84	TSC complex subunit 2	Mus musculus	9-13
14561707-3	2003	Tsc2(-/-)TP53(-/-) cells, as well as tumors from Tsc2(+/-) mice, display an mTOR-activation signature with constitutive activation of S6K, which is reverted by treatment with rapamycin.	Sirolimus	175-184	TSC complex subunit 2	Mus musculus	0-4
14561707-4	2003	Rapamycin also reverts a growth advantage of Tsc2(-/-)TP53(-/-) cells.	Sirolimus	0-9	TSC complex subunit 2	Mus musculus	45-49
10891372-6	2000	Mutation of the core motif of the EBS demonstrated that EBS positively regulates transcription of both mNthl1 and mTsc2 genes.	ethylbenzene	34-37	TSC complex subunit 2	Mus musculus	114-119
10891372-6	2000	Mutation of the core motif of the EBS demonstrated that EBS positively regulates transcription of both mNthl1 and mTsc2 genes.	ethylbenzene	56-59	TSC complex subunit 2	Mus musculus	114-119
15150095-2	2004	We demonstrate a dramatic decrease of IFN-gamma expression in tumors and mouse embryo fibroblast cell lines that lack either Tsc1 or Tsc2, which is reversed by rapamycin (mammalian target of rapamycin inhibitor) therapy.	Sirolimus	160-169	TSC complex subunit 2	Mus musculus	133-137
10584558-8	1999	In contrast to other polymorphisms within the Tsc-2 coding region which did not result in amino acid changes in Tsc-2 gene product tuberin, this mutation substituted a phenylalanine for a conserved cysteine in tw5 tuberin.	Phenylalanine	168-181	TSC complex subunit 2	Mus musculus	46-51
34279736-8	2021	In contrast, frequencies of both mIPSCs and sIPCSs were suppressed by baclofen stronger in Tsc2+/- neurons than in WT ones, whereas CGP55845 significantly increased (m/s)IPSC frequencies only in WT cells.	Baclofen	70-78	TSC complex subunit 2	Mus musculus	91-95
34822420-2	2021	This study aims to investigate the contribution of magnesium-restriction to the development of NAFLD.	Magnesium	51-60	TSC complex subunit 2	Mus musculus	95-100
34822420-11	2021	Accordingly, our data suggest that magnesium is involved in hepatic inflammatory processes and hepatocyte enlargement, key histological features of human NAFLD, and may therefore contribute to development and progression of the disease.	Magnesium	35-44	TSC complex subunit 2	Mus musculus	154-159
34081952-1	2021	RATIONALE: The nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) and its primary inhibitor, tuberin (TSC2), are cues for the development of cardiac hypertrophy.	Sirolimus	54-63	TSC complex subunit 2	Mus musculus	110-117
34081952-1	2021	RATIONALE: The nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) and its primary inhibitor, tuberin (TSC2), are cues for the development of cardiac hypertrophy.	Sirolimus	54-63	TSC complex subunit 2	Mus musculus	119-123
34944575-6	2021	5-azacytidine restored tuberin expression with a reduction of MMP-2 and MMP-7 levels and inhibits motility, similarly to rapamycin and anti-EGFR antibody.	Azacitidine	0-13	TSC complex subunit 2	Mus musculus	23-30
34150002-13	2021	DNMT1 was increased while STAT3, PTEN and TSC2 were decreased by 5-AZA-DC.	Azacitidine	65-70	TSC complex subunit 2	Mus musculus	42-46
34253722-1	2021	Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	128-137	TSC complex subunit 2	Mus musculus	54-58
33948987-8	2021	In summary, PYOs treatment remarkably improved NAFLD via a specific molecular mechanism and reshaped the cecal microbiota.	pyos	12-16	TSC complex subunit 2	Mus musculus	47-52
33948987-0	2021	Porphyran-derived oligosaccharides alleviate NAFLD and related cecal microbiota dysbiosis in mice.	Oligosaccharides	18-34	TSC complex subunit 2	Mus musculus	45-50
33948987-2	2021	In this study, we evaluated the potential efficacy of porphyran-derived oligosaccharides from Porphyra yezoensis (PYOs) in alleviating nonalcoholic fatty liver disease (NAFLD) and preliminarily clarified the underlying mechanism.	Oligosaccharides	72-88	TSC complex subunit 2	Mus musculus	169-174
35121635-9	2022	Oral administration of lonafarnib increased unfarnesylated protein levels without affecting mTORC1and MAP kinase signalings, and restored dendritic spine morphology in the hippocampi of male Tsc2+/- mice.	lonafarnib	23-33	TSC complex subunit 2	Mus musculus	191-195
35609854-2	2022	Although fructose intake has been considered to be a progressive factor in the pathophysiology of NAFLD, it remains unclear how fructose contributes to hepatocellular damage during lipotoxicity.	Fructose	9-17	TSC complex subunit 2	Mus musculus	98-103
35121635-11	2022	These results suggest that the Rheb1 activation may be responsible for synaptic abnormalities and memory impairments in Tsc2+/- mice, and its inhibition by lonafarnib could provide insight into potential treatment options for TSC-associated neuropsychiatric disorders (TANDs).SIGNIFICANCE STATEMENTTuberous sclerosis complex (TSC) is an autosomal dominant disease that causes neuropsychiatric symptoms, including intractable epilepsy, intellectual disability (ID) and autism.	lonafarnib	156-166	TSC complex subunit 2	Mus musculus	120-124
35198900-4	2022	In this study, we generated a doxycycline-inducible MHC-I and -II antigen-expressing HCC cell line which allowed us to investigate tumor antigen-specific T cell response in two NAFLD mouse models.	Doxycycline	30-41	TSC complex subunit 2	Mus musculus	177-182
35405942-0	2022	Investigation of the Effect of Curcumin on Protein Targets in NAFLD Using Bioinformatic Analysis.	Curcumin	31-39	TSC complex subunit 2	Mus musculus	62-67
35405942-5	2022	Here, bioinformatic tools, gene-drug and gene-disease databases were utilized to explore targets, interactions, and pathways through which curcumin could impact NAFLD.	Curcumin	139-147	TSC complex subunit 2	Mus musculus	161-166
35405942-15	2022	CONCLUSION: Curcumin may improve, or inhibit, progression of NAFLD through activation/inhibition of NAFLD-related genes.	Curcumin	12-20	TSC complex subunit 2	Mus musculus	61-66
35405942-15	2022	CONCLUSION: Curcumin may improve, or inhibit, progression of NAFLD through activation/inhibition of NAFLD-related genes.	Curcumin	12-20	TSC complex subunit 2	Mus musculus	100-105
33888601-6	2021	TSC2-deficient cells showed a striking increase in the number of SGs after thermal shock and arsenite treatment relative to Tsc2-expressing cells.	arsenite	93-101	TSC complex subunit 2	Mus musculus	0-4
34999833-9	2022	Finally, the loss of Yap/Taz increased the distribution of myelin basic protein in Tsc2 cKO animals, consistent with an improvement in myelination.	CKO	88-91	TSC complex subunit 2	Mus musculus	83-87
33593821-3	2021	To determine how the metabolic vulnerabilities of TSC2-deficient cells can be targeted, we performed a high throughput screen utilizing the "Repurposing" library at the Broad Institute, with or without the autophagy inhibitor chloroquine.	Chloroquine	226-237	TSC complex subunit 2	Mus musculus	50-54
33882264-11	2021	Using an immuno-competent Tsc2 null murine homograft model, sodium cromoglycate markedly reduced mast cell activation and Tsc2 null lung tumour burden (vehicle: 32.5.3%+-23.6 and cromoglycate: 5.5%+-4.3.	Cromolyn Sodium	60-79	TSC complex subunit 2	Mus musculus	26-30
33882264-11	2021	Using an immuno-competent Tsc2 null murine homograft model, sodium cromoglycate markedly reduced mast cell activation and Tsc2 null lung tumour burden (vehicle: 32.5.3%+-23.6 and cromoglycate: 5.5%+-4.3.	Cromolyn Sodium	60-79	TSC complex subunit 2	Mus musculus	122-126
33882264-11	2021	Using an immuno-competent Tsc2 null murine homograft model, sodium cromoglycate markedly reduced mast cell activation and Tsc2 null lung tumour burden (vehicle: 32.5.3%+-23.6 and cromoglycate: 5.5%+-4.3.	Cromolyn Sodium	67-79	TSC complex subunit 2	Mus musculus	26-30
33882264-11	2021	Using an immuno-competent Tsc2 null murine homograft model, sodium cromoglycate markedly reduced mast cell activation and Tsc2 null lung tumour burden (vehicle: 32.5.3%+-23.6 and cromoglycate: 5.5%+-4.3.	Cromolyn Sodium	67-79	TSC complex subunit 2	Mus musculus	122-126
33593821-4	2021	Ritanserin, an inhibitor of diacylglycerol kinase alpha (DGKA), was identified as a selective inhibitor of proliferation of Tsc2-/- MEFs, with no impact on Tsc2+/+ MEFs.	Ritanserin	0-10	TSC complex subunit 2	Mus musculus	124-128
33593821-6	2021	PA levels were increased 5-fold in Tsc2-/- MEFs compared to Tsc2+/+ MEFs, and treatment of Tsc2-/- MEFs with ritanserin led to depletion of PA as well as rewiring of phospholipid metabolism.	Phosphatidic Acids	0-2	TSC complex subunit 2	Mus musculus	35-39
33593821-6	2021	PA levels were increased 5-fold in Tsc2-/- MEFs compared to Tsc2+/+ MEFs, and treatment of Tsc2-/- MEFs with ritanserin led to depletion of PA as well as rewiring of phospholipid metabolism.	Ritanserin	109-119	TSC complex subunit 2	Mus musculus	35-39
33593821-6	2021	PA levels were increased 5-fold in Tsc2-/- MEFs compared to Tsc2+/+ MEFs, and treatment of Tsc2-/- MEFs with ritanserin led to depletion of PA as well as rewiring of phospholipid metabolism.	Ritanserin	109-119	TSC complex subunit 2	Mus musculus	60-64
33593821-6	2021	PA levels were increased 5-fold in Tsc2-/- MEFs compared to Tsc2+/+ MEFs, and treatment of Tsc2-/- MEFs with ritanserin led to depletion of PA as well as rewiring of phospholipid metabolism.	Ritanserin	109-119	TSC complex subunit 2	Mus musculus	60-64
33593821-8	2021	Ritanserin decreased macropinocytic uptake of albumin, limited the number of lysosomes, and reduced lysosomal activity in Tsc2-/- MEFs.	Ritanserin	0-10	TSC complex subunit 2	Mus musculus	122-126
33523984-8	2021	This demonstrates the potential of treating life-threatening TSC2 lesions with a single intravenous injection of AAV9-cTuberin.	aav9-ctuberin	113-126	TSC complex subunit 2	Mus musculus	61-65
33401933-4	2021	This can be circumvented by regulating one serine (S1365) on tuberous sclerosis complex (TSC2) to achieve bi-directional mTORC1 modulation but only with TCS2-regulated co-stimulation.	Serine	43-49	TSC complex subunit 2	Mus musculus	89-93
33401933-4	2021	This can be circumvented by regulating one serine (S1365) on tuberous sclerosis complex (TSC2) to achieve bi-directional mTORC1 modulation but only with TCS2-regulated co-stimulation.	Serine	43-49	TSC complex subunit 2	Mus musculus	153-157
33401933-14	2021	Conclusions: TSC2-S1365 phosphorylation status regulates myocardial substrate utilization, and its decline activates mTORC1 biasing metabolism away from fatty acid oxidation to glycolysis to confer protection against IR.	Fatty Acids	153-163	TSC complex subunit 2	Mus musculus	13-17
32781001-9	2020	AA levels and rapamycin differentially modulate S6 and 4E-BP1 phosphorylation and mTOR lysosomal localization in neurons following Tsc2 KO versus Depdc5 KO.	Sirolimus	14-23	TSC complex subunit 2	Mus musculus	131-135
32530070-5	2021	We previously used curcumin, a diet-derived mTOR inhibitor, which possesses both anti-inflammatory and anti-proliferative properties, to improve learning and memory deficits in Tsc2+/- mice.	Curcumin	19-27	TSC complex subunit 2	Mus musculus	177-181
32530070-7	2021	In this study, we confirmed that the impaired recognition memory and increased anxiety-like behavior in Tsc2+/- mice can be reversed by curcumin treatment.	Curcumin	136-144	TSC complex subunit 2	Mus musculus	104-108
32530070-9	2021	Finally, the mTOR complex 1 hyperactivity was found in the cortex and hippocampus, coinciding with abnormal cortical myelination and increased glial fibrillary acidic protein expression in the hippocampal CA1 of Tsc2+/- mice, both of which can be rescued with curcumin treatment.	Curcumin	260-268	TSC complex subunit 2	Mus musculus	212-216
32393148-1	2020	Rationale: Stimulated protein kinase G-1alpha (PKG1alpha) phosphorylates tuberous sclerosis complex 2 (TSC2) at serine 1365, potently suppressing mTORC1 activation by neuro-hormonal and hemodynamic stress.	Serine	112-118	TSC complex subunit 2	Mus musculus	73-101
33159078-6	2020	Mesenchymal-restricted deletion of Tsc2 in the mouse lung produces a mTORC1-driven pulmonary phenotype, with a progressive disruption of alveolar structure, a decline in pulmonary function, increase of rapamycin-sensitive expression of WNT ligands, and profound female-specific changes in mesenchymal and epithelial lung cell gene expression.	Sirolimus	202-211	TSC complex subunit 2	Mus musculus	35-39
33054857-5	2020	RESULTS: Ribosome profiling reveals that in Tsc2+/- mouse hippocampal slices, the expression of several mRNAs was dysregulated: terminal oligopyrimidine (TOP)-containing mRNAs decreased, while FMRP-binding targets increased.	oligopyrimidine	137-152	TSC complex subunit 2	Mus musculus	44-48
32912901-0	2020	AMPK regulation of Raptor and TSC2 mediate metformin effects on transcriptional control of anabolism and inflammation.	Metformin	43-52	TSC complex subunit 2	Mus musculus	30-34
32912901-5	2020	Metformin treatment of primary hepatocytes and intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for both the translational and transcriptional response to metformin.	Metformin	0-9	TSC complex subunit 2	Mus musculus	111-115
32512010-0	2020	High glucose-induced ROS accumulation is a critical regulator of ERK1/2-Akt-tuberin-mTOR signalling in RGC-5 cells.	Glucose	5-12	TSC complex subunit 2	Mus musculus	76-83
32512010-8	2020	Collectively, our results demonstrates that HG-induced over production of ROS, disrupts the antioxidant defence mechanism and mitochondrial dysfunction, leading to alterations of inflammatory mediators and neurodegenerative markers through the ERK1/2-Akt-tuberin-mTOR dependent signalling pathway in RGC-5 cells.	ros	74-77	TSC complex subunit 2	Mus musculus	255-262
32588887-2	2020	TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling.	Sirolimus	130-139	TSC complex subunit 2	Mus musculus	58-62
32588887-3	2020	Using a mouse model of TSC (Tsc2-RG) in which the Tsc2 gene is deleted in radial glial precursors and their neuronal and glial descendants, we observed increased ornithine decarboxylase (ODC) enzymatic activity and concentration of its product, putrescine.	Putrescine	245-255	TSC complex subunit 2	Mus musculus	28-32
32588887-3	2020	Using a mouse model of TSC (Tsc2-RG) in which the Tsc2 gene is deleted in radial glial precursors and their neuronal and glial descendants, we observed increased ornithine decarboxylase (ODC) enzymatic activity and concentration of its product, putrescine.	Putrescine	245-255	TSC complex subunit 2	Mus musculus	50-54
32588887-5	2020	We observed that decreasing ODC activity and putrescine levels in Tsc2-RG mice worsened many of the neurodevelopmental phenotypes, including brain growth and neuronal migration defects, astrogliosis and oxidative stress.	Putrescine	45-55	TSC complex subunit 2	Mus musculus	66-70
32588887-6	2020	These data suggest a protective effect of increased ODC activity and elevated putrescine that modify the phenotype in this developmental Tsc2-RG model.	Putrescine	78-88	TSC complex subunit 2	Mus musculus	137-141
33159078-1	2020	Lymphangioleiomyomatosis (LAM) is a rare fatal cystic lung disease due to bi-allelic inactivating mutations in tuberous sclerosis complex (TSC1/TSC2) genes coding for suppressors of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	208-217	TSC complex subunit 2	Mus musculus	144-148
32705128-6	2020	Short (1 h) preincubation of P25-30 Tsc2+/- slices with baclofen restores the GABABR-mediated inhibition and reduces network excitability.	Baclofen	56-64	TSC complex subunit 2	Mus musculus	36-40
32705128-6	2020	Short (1 h) preincubation of P25-30 Tsc2+/- slices with baclofen restores the GABABR-mediated inhibition and reduces network excitability.	gababr	78-84	TSC complex subunit 2	Mus musculus	36-40
32965772-10	2020	Taken conjointly, this study provides evidence reporting that MSC-secreted EVs carry TGF-beta1 to promote M2 polarization of macrophages via modulation of the miR-132/Mycbp2/TSC2 axis.	EVS	75-78	TSC complex subunit 2	Mus musculus	174-178
32393148-1	2020	Rationale: Stimulated protein kinase G-1alpha (PKG1alpha) phosphorylates tuberous sclerosis complex 2 (TSC2) at serine 1365, potently suppressing mTORC1 activation by neuro-hormonal and hemodynamic stress.	Serine	112-118	TSC complex subunit 2	Mus musculus	103-107
32045362-3	2020	The LAM cell origin remains unknown; however, previous work demonstrated that Tsc2 inactivation in the mouse uterus induced estrogen-dependent myometrial tumors with nearly all features of LAM.	Estrogens	124-132	TSC complex subunit 2	Mus musculus	78-82
32346419-7	2020	In the present study, it was indicated that the PTEN inhibitor, hydroxyl(oxo)vanadium 3-hydroxypiridine-2-carboxylic acid (VO-OHpic), suppressed proliferation and growth of TSC2- / - murine embryonic fibroblasts (MEFs) by further inhibiting autophagy of cells.	hydroxyl(oxo)vanadium 3-hydroxypiridine-2-carboxylic acid	64-121	TSC complex subunit 2	Mus musculus	173-177
32346419-7	2020	In the present study, it was indicated that the PTEN inhibitor, hydroxyl(oxo)vanadium 3-hydroxypiridine-2-carboxylic acid (VO-OHpic), suppressed proliferation and growth of TSC2- / - murine embryonic fibroblasts (MEFs) by further inhibiting autophagy of cells.	VO-OHpic	123-131	TSC complex subunit 2	Mus musculus	173-177
32375878-2	2020	TSC1 and TSC2 are repressors of the mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis.	Sirolimus	58-67	TSC complex subunit 2	Mus musculus	9-13
32045362-7	2020	RNA and protein analysis of Tsc2-null myometrial tumors and xenografts demonstrate high expression and activity of the serine protease neutrophil elastase (NE), with selective qPCR studies indicating a stromal origin of the NE.	cholecystokinin C-terminal flanking peptide	119-125	TSC complex subunit 2	Mus musculus	28-32
30680920-5	2019	Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin results in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut-liver axis alteration blockage in these receivers.	Quercetin	194-203	TSC complex subunit 2	Mus musculus	55-60
32063747-0	2020	Zoledronic acid inhibits TSC2-null cell tumor growth via RhoA/YAP signaling pathway in mouse models of lymphangioleiomyomatosis.	zol	0-15	TSC complex subunit 2	Mus musculus	25-29
32063747-1	2020	Background: This study is to investigate the effects of zoledronic acid (ZA) on TSC2-null cell proliferation and on the tumor progression and recurrence in mouse models of lymphangioleiomyomatosis (LAM).	zol	56-71	TSC complex subunit 2	Mus musculus	80-84
32063747-1	2020	Background: This study is to investigate the effects of zoledronic acid (ZA) on TSC2-null cell proliferation and on the tumor progression and recurrence in mouse models of lymphangioleiomyomatosis (LAM).	zol	73-75	TSC complex subunit 2	Mus musculus	80-84
32063747-6	2020	Results: ZA prevented the growth of TSC2-null cells both in culture and in LAM mouse models.	zol	9-11	TSC complex subunit 2	Mus musculus	36-40
32063747-7	2020	Compared with rapamycin, ZA more effectively promoted the apoptosis of TSC2-null cells.	zol	25-27	TSC complex subunit 2	Mus musculus	71-75
31078684-6	2019	Loss of either Tsc1 or Tsc2 from astrocytes resulted in a marked increase in Aqp4 expression which was sensitive to mTORC1 inhibition with rapamycin.	Sirolimus	139-148	TSC complex subunit 2	Mus musculus	23-27
31207499-6	2019	Both AZD2014 and rapamycin potently suppressed EMT of renal tumors and effectively blocked tumor progression in Tsc2+/- mice.	vistusertib	5-12	TSC complex subunit 2	Mus musculus	112-116
31207499-6	2019	Both AZD2014 and rapamycin potently suppressed EMT of renal tumors and effectively blocked tumor progression in Tsc2+/- mice.	Sirolimus	17-26	TSC complex subunit 2	Mus musculus	112-116
30928642-6	2019	We found that antagonists that preferentially block tonic activity as found at eNMDARs, particularly the newer drug NitroSynapsin, provide biological and statistically significant improvement in Tsc2+/- phenotypes.	Nitromemantine	116-129	TSC complex subunit 2	Mus musculus	195-199
30928642-8	2019	Deficits in hippocampal long-term potentiation (LTP), histological loss of synapses, and behavioral fear conditioning in Tsc2+/- mice were all improved after treatment with NitroSynapsin.	Nitromemantine	173-186	TSC complex subunit 2	Mus musculus	121-125
32191726-6	2020	Rapamycin attenuated podocyte dysfunction and extends survival in Tsc2Deltapodocyte mice.	Sirolimus	0-9	TSC complex subunit 2	Mus musculus	66-70
32063747-9	2020	Conclusion: ZA promotes cell apoptosis in TSC2-null cells through the RhoA/YAP signaling pathway.	zol	12-14	TSC complex subunit 2	Mus musculus	42-46
31717842-9	2019	Moreover, PA also regulated the NAFLD signaling pathway.	Protactinium	10-12	TSC complex subunit 2	Mus musculus	32-37
31717842-11	2019	Taken together, our results demonstrate that PA can improve the liver function of NAFLD mice, regulating blood lipids, reducing liver-fat accumulation, and regulating lipid metabolism.	Protactinium	45-47	TSC complex subunit 2	Mus musculus	82-87
31441223-4	2019	Mechanistically, we show that iron overload leads to a decrease in Akt-mediated repression of tuberous sclerosis complex (TSC2) and Rheb-mediated mTORC1 activation on autolysosomes, thereby inhibiting autophagic-lysosome regeneration.	Iron	30-34	TSC complex subunit 2	Mus musculus	122-126
31207499-0	2019	Allosteric and ATP-Competitive Inhibitors of mTOR Effectively Suppress Tumor Progression-Associated Epithelial-Mesenchymal Transition in the Kidneys of Tsc2+/- Mice.	Adenosine Triphosphate	15-18	TSC complex subunit 2	Mus musculus	152-156
30508035-7	2019	Intra-glomerular reactive oxygen species (ROS) levels measured by dihydroethidium florescence showed significant increases in ROS production in irradiated Tsc2+/- mice compared with non-irradiated animals.	Reactive Oxygen Species	17-40	TSC complex subunit 2	Mus musculus	155-159
30508035-7	2019	Intra-glomerular reactive oxygen species (ROS) levels measured by dihydroethidium florescence showed significant increases in ROS production in irradiated Tsc2+/- mice compared with non-irradiated animals.	Reactive Oxygen Species	42-45	TSC complex subunit 2	Mus musculus	155-159
30508035-7	2019	Intra-glomerular reactive oxygen species (ROS) levels measured by dihydroethidium florescence showed significant increases in ROS production in irradiated Tsc2+/- mice compared with non-irradiated animals.	dihydroethidium	66-81	TSC complex subunit 2	Mus musculus	155-159
30508035-7	2019	Intra-glomerular reactive oxygen species (ROS) levels measured by dihydroethidium florescence showed significant increases in ROS production in irradiated Tsc2+/- mice compared with non-irradiated animals.	Reactive Oxygen Species	126-129	TSC complex subunit 2	Mus musculus	155-159
30680920-5	2019	Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin results in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut-liver axis alteration blockage in these receivers.	Quercetin	194-203	TSC complex subunit 2	Mus musculus	258-263
30668362-2	2019	Recent studies suggest that curcumin inhibit mTOR activity in vitro, which prompts us to investigate curcumin function as a new class of mTOR inhibitor suitable for tuberous sclerosis complex (TSC) treatment.	Curcumin	101-109	TSC complex subunit 2	Mus musculus	193-196
31182914-0	2019	Feedback Activation of SGK3 and AKT Contributes to Rapamycin Resistance by Reactivating mTORC1/4EBP1 Axis via TSC2 in Breast Cancer.	Sirolimus	51-60	TSC complex subunit 2	Mus musculus	110-114
30816188-6	2019	We developed the first Tsc2-null rapamycin-resistant cell line, ELT3-245, which is highly tumorigenic in mice, and refractory to rapamycin treatment.	Sirolimus	33-42	TSC complex subunit 2	Mus musculus	23-27
30816216-2	2019	Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models.	Sirolimus	123-132	TSC complex subunit 2	Mus musculus	231-235
30728291-4	2019	By studying human and mouse cells with defective or absent TSC2, we show that complete loss of TSC2 causes an increase in glycogen synthesis through mTORC1 hyperactivation and subsequent inactivation of glycogen synthase kinase 3beta (GSK3beta), a negative regulator of glycogen synthesis.	Glycogen	122-130	TSC complex subunit 2	Mus musculus	95-99
30728291-4	2019	By studying human and mouse cells with defective or absent TSC2, we show that complete loss of TSC2 causes an increase in glycogen synthesis through mTORC1 hyperactivation and subsequent inactivation of glycogen synthase kinase 3beta (GSK3beta), a negative regulator of glycogen synthesis.	Glycogen	203-211	TSC complex subunit 2	Mus musculus	95-99
30728291-5	2019	Specific TSC2 pathogenic mutations, however, result in elevated glycogen levels with no changes in mTORC1 or GSK3beta activities.	Glycogen	64-72	TSC complex subunit 2	Mus musculus	9-13
30668362-3	2019	PURPOSE: We aim to investigate the efficacy of curcumin in the treatment of TSC related manifestations in animal model.	Curcumin	47-55	TSC complex subunit 2	Mus musculus	76-79
30668362-4	2019	STUDY DESIGN: Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice.	Curcumin	26-34	TSC complex subunit 2	Mus musculus	100-103
30668362-4	2019	STUDY DESIGN: Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice.	Curcumin	26-34	TSC complex subunit 2	Mus musculus	130-134
30622053-6	2019	Following 2 months of treatment of Tsc2+/- mice from the age of 12 months, combination of 3-BrPA and CB-839 significantly reduced overall size and cellular areas of all renal lesions (cystic/papillary adenomas and solid carcinomas), but neither alone did.	bromopyruvate	90-96	TSC complex subunit 2	Mus musculus	35-39
30461191-6	2019	Furthermore, follicular development disorder induced by nano TiO2 was associated with upregulation of TGF-beta1, TGF-betaR1, PTEN, and Foxo3a involved in cell growth and apoptosis and downregulation of several growth factors (PI3K, AKT, p-mTOR, p70S6K, p-p70S6K1, rpS6, p-rpS6, TSC1, and TSC2) in mouse ovaries.	titanium dioxide	61-65	TSC complex subunit 2	Mus musculus	288-292
30622053-3	2019	Activation of mTOR complex 1 (mTORC1) causes addiction to glucose and glutamine in Tsc1-/-or Tsc2-/- mouse embryonic fibroblasts (MEFs).	Glutamine	70-79	TSC complex subunit 2	Mus musculus	93-97
30622053-6	2019	Following 2 months of treatment of Tsc2+/- mice from the age of 12 months, combination of 3-BrPA and CB-839 significantly reduced overall size and cellular areas of all renal lesions (cystic/papillary adenomas and solid carcinomas), but neither alone did.	CB-839	101-107	TSC complex subunit 2	Mus musculus	35-39
30622053-4	2019	Blocking of glutamine anaplerosis in combination with glycolytic inhibition causes significant cell death in Tsc2-/- but not Tsc2+/+ MEFs.	Glutamine	12-21	TSC complex subunit 2	Mus musculus	109-113
30700906-6	2019	Here we show that phosphorylation or gain- or loss-of-function mutations at either of two adjacent serine residues in TSC2 (S1365 and S1366 in mice; S1364 and S1365 in humans) can bidirectionally control mTORC1 activity stimulated by growth factors or haemodynamic stress, and consequently modulate cell growth and autophagy.	Serine	99-105	TSC complex subunit 2	Mus musculus	118-122
30054282-9	2018	Interestingly, [18F]FCH-PET imaging of TSC2-deficient xenografts in ovariectomized mice also showed a significant decrease in tumor SUV.	fluorocholine	20-23	TSC complex subunit 2	Mus musculus	39-43
28844017-4	2017	Previous studies have demonstrated that atorvastatin selectively suppressed growth and proliferation of mouse Tsc2 null embryonic fibroblasts through inhibition of mTOR.	Atorvastatin	40-52	TSC complex subunit 2	Mus musculus	110-114
29396625-5	2018	Hedgehog signaling was restored in Tsc1-/- cells after exogenous expression of Gli2, whereas rapamycin restored HH signaling in Tsc2-/- cells.	Sirolimus	93-102	TSC complex subunit 2	Mus musculus	128-132
29635516-10	2018	Treatment of Tsc2+/- mice with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine, to reduce putrescine synthesis dose-dependently reduced hippocampal astrogliosis.	Eflornithine	69-98	TSC complex subunit 2	Mus musculus	13-17
29635516-10	2018	Treatment of Tsc2+/- mice with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine, to reduce putrescine synthesis dose-dependently reduced hippocampal astrogliosis.	Putrescine	110-120	TSC complex subunit 2	Mus musculus	13-17
29364507-6	2018	The value of lambda was higher in Tsc2+/- mice, indicating that a greater fraction of leucine in the tissue precursor pool for protein synthesis is derived from the plasma compared to controls, consistent with reduced rates of protein degradation.	Leucine	86-93	TSC complex subunit 2	Mus musculus	34-38
29720580-6	2018	AZD8055, but not everolimus, potently prevented cells from transitioning from G1 phase to S phase in TSC2-high-expressing HCC cells.	(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol	0-7	TSC complex subunit 2	Mus musculus	101-105
29720580-12	2018	AZD8055 showed stronger antitumor activity than everolimus in TSC2-high-expressing HCC cells.	(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol	0-7	TSC complex subunit 2	Mus musculus	62-66
29720580-12	2018	AZD8055 showed stronger antitumor activity than everolimus in TSC2-high-expressing HCC cells.	Everolimus	48-58	TSC complex subunit 2	Mus musculus	62-66
29491408-3	2018	Downregulation of tuberin (protein encoded by TSC2 gene) in renal proximal tubular epithelial cells significantly increased ROS concomitant with enhanced Nox4.	Reactive Oxygen Species	124-127	TSC complex subunit 2	Mus musculus	18-25
29491408-3	2018	Downregulation of tuberin (protein encoded by TSC2 gene) in renal proximal tubular epithelial cells significantly increased ROS concomitant with enhanced Nox4.	Reactive Oxygen Species	124-127	TSC complex subunit 2	Mus musculus	46-50
29491408-9	2018	Using a xenograft model from tuberin-null tubular cells in nude mice, both anti-sense Nox4 and GKT137831, a specific inhibitor of Nox1/4, significantly inhibited the tumor growth.	setanaxib	95-104	TSC complex subunit 2	Mus musculus	29-36
28972182-7	2017	However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC.	Sirolimus	9-18	TSC complex subunit 2	Mus musculus	55-59
28972182-7	2017	However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC.	Sirolimus	9-18	TSC complex subunit 2	Mus musculus	94-98
28972182-9	2017	Moreover, rapamycin-enhanced migration of TSC2-null cells was inhibited by the uPA inhibitor UK122, dexamethasone, and a FOXO inhibitor.	CHEMBL1945236	93-98	TSC complex subunit 2	Mus musculus	42-46
28972182-9	2017	Moreover, rapamycin-enhanced migration of TSC2-null cells was inhibited by the uPA inhibitor UK122, dexamethasone, and a FOXO inhibitor.	Dexamethasone	100-113	TSC complex subunit 2	Mus musculus	42-46
28808237-1	2017	Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1).	Sirolimus	179-188	TSC complex subunit 2	Mus musculus	104-108
28473248-9	2017	Moreover, autophagy inhibitor 3-MA could simulate the effects of TSC2 siRNA while autophagy inducer rapamycin could mimic the effects of raptor siRNA, suggesting that the beneficial effects of mTORC1 deletion were associated with autophagy induction.	3-methyladenine	30-34	TSC complex subunit 2	Mus musculus	65-69
28092822-0	2017	Combination of Everolimus with Sorafenib for Solid Renal Tumors in Tsc2+/- Mice Is Superior to Everolimus Alone.	Everolimus	15-25	TSC complex subunit 2	Mus musculus	67-71
28367235-5	2017	By analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), we found that loss of TSC1 or TSC2 led to a decreased sensitivity to MK-2206, a novel allosteric Akt inhibitor.	MK 2206	137-144	TSC complex subunit 2	Mus musculus	22-26
28367235-5	2017	By analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), we found that loss of TSC1 or TSC2 led to a decreased sensitivity to MK-2206, a novel allosteric Akt inhibitor.	MK 2206	137-144	TSC complex subunit 2	Mus musculus	98-102
28092822-8	2017	Treatment of 11-month-old Tsc2+/- mice for 2 months with a combination of everolimus and sorafenib significantly reduced the number and size of solid renal tumors, whereas everolimus or sorafenib alone did not.	Everolimus	74-84	TSC complex subunit 2	Mus musculus	26-30
28512249-3	2017	Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH).	Glutamine	94-103	TSC complex subunit 2	Mus musculus	54-58
28512249-3	2017	Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH).	Glutamic Acid	105-114	TSC complex subunit 2	Mus musculus	54-58
28512249-3	2017	Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH).	Glutathione	120-131	TSC complex subunit 2	Mus musculus	54-58
28512249-3	2017	Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH).	Glutathione	133-136	TSC complex subunit 2	Mus musculus	54-58
28512249-7	2017	These mitochondrial phenotypes were rescued by addition of exogenous GSH and overexpression of Sod2, which suppressed indices of mitochondrial damage and promoted growth of Tsc2-null cells.	Glutathione	69-72	TSC complex subunit 2	Mus musculus	173-177
28512249-8	2017	Finally, p62 depletion sensitized Tsc2-null cells to both oxidative stress and direct inhibition of GSH biosynthesis by buthionine sulfoximine.	Glutathione	100-103	TSC complex subunit 2	Mus musculus	34-38
28512249-8	2017	Finally, p62 depletion sensitized Tsc2-null cells to both oxidative stress and direct inhibition of GSH biosynthesis by buthionine sulfoximine.	Buthionine Sulfoximine	120-142	TSC complex subunit 2	Mus musculus	34-38
28938574-0	2017	The dual PI3K/mTOR inhibitor GSK2126458 is effective for treating solid renal tumours in Tsc2+/- mice through suppression of cell proliferation and induction of apoptosis.	omipalisib	29-39	TSC complex subunit 2	Mus musculus	89-93
28092822-8	2017	Treatment of 11-month-old Tsc2+/- mice for 2 months with a combination of everolimus and sorafenib significantly reduced the number and size of solid renal tumors, whereas everolimus or sorafenib alone did not.	Sorafenib	89-98	TSC complex subunit 2	Mus musculus	26-30
28092822-0	2017	Combination of Everolimus with Sorafenib for Solid Renal Tumors in Tsc2+/- Mice Is Superior to Everolimus Alone.	Sorafenib	31-40	TSC complex subunit 2	Mus musculus	67-71
27278252-9	2016	In addition, treatment of mice deficient in tuberin with rapamycin resulted in significant decrease in all Nox protein expression.	Sirolimus	57-66	TSC complex subunit 2	Mus musculus	44-51
27542907-0	2016	TSC2 N-terminal lysine acetylation status affects to its stability modulating mTORC1 signaling and autophagy.	Lysine	16-22	TSC complex subunit 2	Mus musculus	0-4
27542907-3	2016	This study analyzes tuberous sclerosis complex (TSC2) lysine acetylation, in the regulation of mTORC1 signaling activation, autophagy and cell proliferation.	Lysine	54-60	TSC complex subunit 2	Mus musculus	48-52
27542907-4	2016	Nicotinamide 5mM (a concentration commonly used to inhibit SIRT1), increased TSC2 acetylation in its N-terminal domain, and concomitantly with an augment in its ubiquitination protein status, leading to mTORC1 activation and cell proliferation.	Niacinamide	0-12	TSC complex subunit 2	Mus musculus	77-81
27542907-5	2016	In contrast, resveratrol (RESV), an activator of sirtuins deacetylation activity, avoided TSC2 acetylation, inhibiting mTORC1 signaling and promoting autophagy.	Resveratrol	13-24	TSC complex subunit 2	Mus musculus	90-94
27542907-5	2016	In contrast, resveratrol (RESV), an activator of sirtuins deacetylation activity, avoided TSC2 acetylation, inhibiting mTORC1 signaling and promoting autophagy.	Resveratrol	26-30	TSC complex subunit 2	Mus musculus	90-94
27542907-12	2016	This study provides, for the first time, a relationship between TSC2 lysine acetylation status and its stability, representing a novel mechanism for regulating mTORC1 pathway.	Lysine	69-75	TSC complex subunit 2	Mus musculus	64-68
27023784-11	2016	The upregulation of autophagic flux by trehalose treatment attenuated the cardiac phenotypes such as cardiac dysfunction and structural abnormalities of mitochondria in TSC2-/- hearts.	Trehalose	39-48	TSC complex subunit 2	Mus musculus	169-173
26935540-0	2016	NQO1 Deficiency Leads Enhanced Autophagy in Cisplatin-Induced Acute Kidney Injury Through the AMPK/TSC2/mTOR Signaling Pathway.	Cisplatin	44-53	TSC complex subunit 2	Mus musculus	99-103
26860957-5	2016	The increase in levels of inflammatory cytokines/chemokines corresponds to increased levels of ROS/RNS, which is accompanied by increased activities of Akt, ERK1/2, tuberin, down regulation of 8-oxoG-DNA glycosylase (OGG1), and increase in 8-hydroxydeoxyguanosine (8-OHdG) accumulation in DNA.	ros	95-98	TSC complex subunit 2	Mus musculus	165-172
26860957-7	2016	Pretreatment of antioxidants caused decrease in the levels of ROS/RNS leads to an increase in the levels of antioxidants, decrease in biomolecules damage, alterations in Akt, ERK1/2, tuberin, upregulation of OGG1, and decrease in 8-OHdG accumulations in DNA.	ros	62-65	TSC complex subunit 2	Mus musculus	183-190
26860957-7	2016	Pretreatment of antioxidants caused decrease in the levels of ROS/RNS leads to an increase in the levels of antioxidants, decrease in biomolecules damage, alterations in Akt, ERK1/2, tuberin, upregulation of OGG1, and decrease in 8-OHdG accumulations in DNA.	Radon	66-69	TSC complex subunit 2	Mus musculus	183-190
26854565-6	2016	Using a large-scale, unbiased quantitative proteomic platform, we comprehensively characterized the rapamycin-sensitive secretome in TSC2(-/-) mouse embryonic fibroblasts, and identified IGFBP5 as a secreted, mTORC1 downstream effector protein.	Sirolimus	100-109	TSC complex subunit 2	Mus musculus	133-137
26432869-0	2015	Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth in the mouse model of lymphangioleiomyomatosis.	Axitinib	50-58	TSC complex subunit 2	Mus musculus	68-72
26432869-3	2015	The goals of our study was to determine whether Tsc2 deficiency upregulates VEGF-D, and whether axitinib, the Food and Drug Administration-approved small-molecule inhibitor of VEGF receptor (VEGFR) signaling, will reduce Tsc2-null lung lesion growth in a mouse model of LAM.	Axitinib	96-104	TSC complex subunit 2	Mus musculus	221-225
26432869-5	2015	Progressive growth of Tsc2-null lesions induces recruitment and activation of inflammatory cells and increased nitric oxide production.	Nitric Oxide	111-123	TSC complex subunit 2	Mus musculus	22-26
26432869-7	2015	Importantly, axitinib is an effective inhibitor of Tsc2-null lesion growth and inflammatory cell recruitment, which correlates with reduced VEGF-D levels in serum and lung lining.	Axitinib	13-21	TSC complex subunit 2	Mus musculus	51-55
26432869-8	2015	Our data demonstrate that pharmacological inhibition of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth, attenuates recruitment and activation of inflammatory cells, and reduces VEGF-D levels systemically and in the lung lining.	Axitinib	77-85	TSC complex subunit 2	Mus musculus	95-99
24931163-3	2015	We show that rapamycin reduces HIF-1alpha protein levels, and to a lesser extent VEGF-A levels, in renal cystadenoma cells in a Tsc2+/- mouse model.	Sirolimus	13-22	TSC complex subunit 2	Mus musculus	128-132