PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
33898931-6	2021	Consistent with our earlier findings, the BMMSCs protected MM cells against KHYG-1 and DR5-agonistic antibodies by inducing resistance mechanisms that were largely abrogated by the small molecule FL118, an inhibitor of multiple antiapoptotic proteins including Survivin, Mcl-1, and XIAP.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	196-201	TNF receptor superfamily member 10b	Homo sapiens	87-90
33883175-7	2021	Furthermore, BMMSC-mediated resistance against CAR T cells was effectively modulated by FL118, an inhibitor of anti-apoptotic proteins Survivin, Mcl-1, and XIAP.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	88-93	CXADR pseudogene 1	Homo sapiens	47-50
33898931-6	2021	Consistent with our earlier findings, the BMMSCs protected MM cells against KHYG-1 and DR5-agonistic antibodies by inducing resistance mechanisms that were largely abrogated by the small molecule FL118, an inhibitor of multiple antiapoptotic proteins including Survivin, Mcl-1, and XIAP.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	196-201	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	271-276
33883175-7	2021	Furthermore, BMMSC-mediated resistance against CAR T cells was effectively modulated by FL118, an inhibitor of anti-apoptotic proteins Survivin, Mcl-1, and XIAP.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	88-93	X-linked inhibitor of apoptosis	Homo sapiens	156-160
33898931-6	2021	Consistent with our earlier findings, the BMMSCs protected MM cells against KHYG-1 and DR5-agonistic antibodies by inducing resistance mechanisms that were largely abrogated by the small molecule FL118, an inhibitor of multiple antiapoptotic proteins including Survivin, Mcl-1, and XIAP.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	196-201	X-linked inhibitor of apoptosis	Homo sapiens	282-286
33217967-0	2020	Mutant Kras as a Biomarker Plays a Favorable Role in FL118-Induced Apoptosis, Reactive Oxygen Species (ROS) Production and Modulation of Survivin, Mcl-1 and XIAP in Human Bladder Cancer.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	53-58	KRAS proto-oncogene, GTPase	Homo sapiens	7-11
33389483-6	2021	Moreover, sequential administration of RSV and FL118 led to a significant increase of apoptotic cells, as well as active Caspase-3/7 levels.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	47-52	caspase 3	Homo sapiens	121-132
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	cadherin 2	Homo sapiens	146-156
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	catenin beta 1	Homo sapiens	158-170
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	vimentin	Homo sapiens	172-180
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	snail family transcriptional repressor 1	Homo sapiens	182-187
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	snail family transcriptional repressor 2	Homo sapiens	193-197
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	fibronectin 1	Homo sapiens	251-262
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	twist family bHLH transcription factor 1	Homo sapiens	264-270
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	twist family bHLH transcription factor 2	Homo sapiens	272-278
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	zinc finger E-box binding homeobox 1	Homo sapiens	280-284
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	zinc finger E-box binding homeobox 2	Homo sapiens	290-294
33389483-7	2021	Sequential administration of RSV and FL118 caused TNBC cells accumulating in the G1 phase, and markedly suppressed the mRNA and protein levels of N-cadherin, beta-catenin, Vimentin, Snail, and Slug, and also significantly downregulated mRNA levels of Fibronectin, Twist1, Twist2, Zeb1, and Zeb2 genes, while enhanced the mRNA and protein levels of E-cadherin genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	37-42	cadherin 1	Homo sapiens	348-358
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	165-170	KRAS proto-oncogene, GTPase	Homo sapiens	144-148
33217967-8	2020	Silencing mutant Kras in UMUC3 cells reduced FL118-mediated ROS generation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	45-50	KRAS proto-oncogene, GTPase	Homo sapiens	17-21
33217967-11	2020	Silencing mutant Kras in UMUC3 cell-derived tumors decreases UMUC3 tumor sensitivity to FL118 treatment.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	88-93	KRAS proto-oncogene, GTPase	Homo sapiens	17-21
33217967-12	2020	Together, our studies revealed that mutant Kras is a favorable biomarker for FL118 targeted treatment.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	KRAS proto-oncogene, GTPase	Homo sapiens	43-47
33217967-2	2020	Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	78-83	HRas proto-oncogene, GTPase	Homo sapiens	192-196
33217967-2	2020	Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	78-83	KRAS proto-oncogene, GTPase	Homo sapiens	201-205
33217967-5	2020	FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	poly(ADP-ribose) polymerase 1	Homo sapiens	23-27
33217967-5	2020	FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	X-linked inhibitor of apoptosis	Homo sapiens	82-86
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	35-40	KRAS proto-oncogene, GTPase	Homo sapiens	17-21
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	35-40	poly(ADP-ribose) polymerase 1	Homo sapiens	49-53
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	35-40	X-linked inhibitor of apoptosis	Homo sapiens	95-99
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	35-40	KRAS proto-oncogene, GTPase	Homo sapiens	144-148
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	165-170	KRAS proto-oncogene, GTPase	Homo sapiens	17-21
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	165-170	poly(ADP-ribose) polymerase 1	Homo sapiens	49-53
33217967-6	2020	Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	165-170	X-linked inhibitor of apoptosis	Homo sapiens	95-99
33187360-6	2020	Our results further showed that, like FL118, 12e inhibited cell proliferation resulting from cell cycle arrest and apoptosis by blocking the anti-apoptotic gene transcription of survivin, Mcl-1, Bcl-2, and XIAP in both A549 cells and NCI-H446 cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	38-43	BCL2 apoptosis regulator	Homo sapiens	195-200
33187360-6	2020	Our results further showed that, like FL118, 12e inhibited cell proliferation resulting from cell cycle arrest and apoptosis by blocking the anti-apoptotic gene transcription of survivin, Mcl-1, Bcl-2, and XIAP in both A549 cells and NCI-H446 cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	38-43	X-linked inhibitor of apoptosis	Homo sapiens	206-210
30285798-0	2018	An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	40-45	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	3-8
30555743-4	2018	In this study we demonstrate that combination of a plant-isolated triterpenoid compound AMR-MeOAc with a low concentration of an antiapoptotic protein inhibitor, FL118 exhibited synergistic cytotoxic activity against pancreatic cancer cells with either mutant KRAS (HPAF-II, KRASG12D) or wild type KRAS (BxPC-3, KRASWT).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	162-167	KRAS proto-oncogene, GTPase	Homo sapiens	260-264
30555743-4	2018	In this study we demonstrate that combination of a plant-isolated triterpenoid compound AMR-MeOAc with a low concentration of an antiapoptotic protein inhibitor, FL118 exhibited synergistic cytotoxic activity against pancreatic cancer cells with either mutant KRAS (HPAF-II, KRASG12D) or wild type KRAS (BxPC-3, KRASWT).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	162-167	KRAS proto-oncogene, GTPase	Homo sapiens	275-279
30555743-5	2018	In pancreatic cancer cells with mutant KRASG12D, AMR-MeOAc and FL118 acting together to inhibit the constitutive KRASG12D mutant activity, increase the reactive oxygen species (ROS) formation, apoptosis induction, and decrease of the expression of survivin and XIAP, while strongly inducing Bax.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	63-68	X-linked inhibitor of apoptosis	Homo sapiens	261-265
30555743-5	2018	In pancreatic cancer cells with mutant KRASG12D, AMR-MeOAc and FL118 acting together to inhibit the constitutive KRASG12D mutant activity, increase the reactive oxygen species (ROS) formation, apoptosis induction, and decrease of the expression of survivin and XIAP, while strongly inducing Bax.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	63-68	BCL2 associated X, apoptosis regulator	Homo sapiens	291-294
30555743-7	2018	Additionally, AMR-MeOAc and FL118 alone or in combination inhibited the constitutive activation of NF-kappaB in BxPC-3 cells, which suggests that inhibition of NF-kappaB in BxPC-3 cells by AMR-MeOAc and FL118 may also be a part of the mechanism of action, when pancreatic cancer cells possess wild type KRAS.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	28-33	KRAS proto-oncogene, GTPase	Homo sapiens	303-307
32659366-14	2020	SIGNIFICANCE: FL118 restrains the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provides important evidence in the study on the role of pyroptosis and different tumors.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	14-19	NLR family pyrin domain containing 3	Homo sapiens	89-94
32659366-14	2020	SIGNIFICANCE: FL118 restrains the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provides important evidence in the study on the role of pyroptosis and different tumors.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	14-19	PYD and CARD domain containing	Homo sapiens	95-98
32659366-14	2020	SIGNIFICANCE: FL118 restrains the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provides important evidence in the study on the role of pyroptosis and different tumors.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	14-19	caspase 1	Homo sapiens	99-108
32624224-0	2020	Retraction notice to "FL118 inhibits viability and induces apoptosis of colorectal cancer cells via inactivating the CIP2A/PP2A axis" [Life Sci.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	22-27	cellular inhibitor of PP2A	Homo sapiens	117-122
32624224-0	2020	Retraction notice to "FL118 inhibits viability and induces apoptosis of colorectal cancer cells via inactivating the CIP2A/PP2A axis" [Life Sci.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	22-27	protein phosphatase 2 phosphatase activator	Homo sapiens	123-127
30285798-8	2018	These FL118 efficacy results are consistent with our molecular-targeting data showing that FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment-resistant pancreatic stem-like cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	6-11	ERCC excision repair 6, chromatin remodeling factor	Homo sapiens	192-197
30285798-8	2018	These FL118 efficacy results are consistent with our molecular-targeting data showing that FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment-resistant pancreatic stem-like cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	91-96	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	168-173
30285798-8	2018	These FL118 efficacy results are consistent with our molecular-targeting data showing that FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment-resistant pancreatic stem-like cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	91-96	X-linked inhibitor of apoptosis	Homo sapiens	175-179
30285798-8	2018	These FL118 efficacy results are consistent with our molecular-targeting data showing that FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment-resistant pancreatic stem-like cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	91-96	baculoviral IAP repeat containing 3	Homo sapiens	181-186
30285798-8	2018	These FL118 efficacy results are consistent with our molecular-targeting data showing that FL118 inhibited the expression of multiple antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and ERCC6, a critical regulator of DNA repair, in treatment-resistant pancreatic stem-like cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	91-96	ERCC excision repair 6, chromatin remodeling factor	Homo sapiens	192-197
28337384-4	2017	Accordingly, FL118 selectively inhibits the expression of multiple cancer-associated proteins (survivin, Mcl-1, XIAP, cIAP2, MdmX).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	13-18	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	105-110
29553100-8	2018	FL118 significantly suppressed the expression of vimentin while enhancing the expression of E-cadherin.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	vimentin	Homo sapiens	49-57
29553100-8	2018	FL118 significantly suppressed the expression of vimentin while enhancing the expression of E-cadherin.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	cadherin 1	Homo sapiens	92-102
29553100-10	2018	Taken together, the current results suggest that FL118 inhibited Wnt/beta-catenin signaling, leading to suppressed EMT and decreased migration and invasion of breast cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	49-54	catenin beta 1	Homo sapiens	69-81
29553100-0	2018	FL118, a novel camptothecin analogue, suppressed migration and invasion of human breast cancer cells by inhibiting epithelial-mesenchymal transition via the Wnt/beta-catenin signaling pathway.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	catenin beta 1	Homo sapiens	161-173
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	130-135
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	aldehyde dehydrogenase 1 family member A1	Homo sapiens	137-144
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	POU class 5 homeobox 1	Homo sapiens	146-150
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	phosphoglycolate phosphatase	Homo sapiens	181-185
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	187-192
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	130-135
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	aldehyde dehydrogenase 1 family member A1	Homo sapiens	137-144
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	POU class 5 homeobox 1	Homo sapiens	146-150
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	phosphoglycolate phosphatase	Homo sapiens	181-185
28861158-9	2017	To further demonstrate the inhibitory effect of FL118 on CSCs, we found that FL118 down-regulated the expression of CSCs markers (ABCG2, ALDH1A1, Oct4) and drug resistant proteins (P-gp, ERCC1), suggesting that FL118 may change CSCs phenotype and improve drug-sensitivity of tumor cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	77-82	ERCC excision repair 1, endonuclease non-catalytic subunit	Homo sapiens	187-192
28337384-4	2017	Accordingly, FL118 selectively inhibits the expression of multiple cancer-associated proteins (survivin, Mcl-1, XIAP, cIAP2, MdmX).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	13-18	X-linked inhibitor of apoptosis	Homo sapiens	112-116
28337384-4	2017	Accordingly, FL118 selectively inhibits the expression of multiple cancer-associated proteins (survivin, Mcl-1, XIAP, cIAP2, MdmX).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	13-18	baculoviral IAP repeat containing 3	Homo sapiens	118-123
28337384-4	2017	Accordingly, FL118 selectively inhibits the expression of multiple cancer-associated proteins (survivin, Mcl-1, XIAP, cIAP2, MdmX).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	13-18	MDM4 regulator of p53	Homo sapiens	125-129
26692923-5	2015	Consistent with our previous studies on irinotecan, FL118 exhibited >=25 fold more effectiveness than topotecan at inhibiting cancer cell growth and colony formation; we further showed that although topotecan can inhibit the expression of survivin, Mcl-1, XIAP or cIAP2, its effectiveness is about 10-100 fold weaker than FL118.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	52-57	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	252-257
26692923-5	2015	Consistent with our previous studies on irinotecan, FL118 exhibited >=25 fold more effectiveness than topotecan at inhibiting cancer cell growth and colony formation; we further showed that although topotecan can inhibit the expression of survivin, Mcl-1, XIAP or cIAP2, its effectiveness is about 10-100 fold weaker than FL118.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	52-57	X-linked inhibitor of apoptosis	Homo sapiens	259-263
26692923-9	2015	Given that both P-gp and ABCG2 express in SW620 and HCT-8 cells and FL118 is not a substrate for P-gp and ABCG2, this suggests that FL118 appears to bypass multiple efflux pump protein-induced resistance, which may contribute to FL118 overcoming irinotecan and topotecan resistance in vivo.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	132-137	phosphoglycolate phosphatase	Homo sapiens	16-20
26692923-9	2015	Given that both P-gp and ABCG2 express in SW620 and HCT-8 cells and FL118 is not a substrate for P-gp and ABCG2, this suggests that FL118 appears to bypass multiple efflux pump protein-induced resistance, which may contribute to FL118 overcoming irinotecan and topotecan resistance in vivo.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	132-137	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	25-30
26692923-5	2015	Consistent with our previous studies on irinotecan, FL118 exhibited >=25 fold more effectiveness than topotecan at inhibiting cancer cell growth and colony formation; we further showed that although topotecan can inhibit the expression of survivin, Mcl-1, XIAP or cIAP2, its effectiveness is about 10-100 fold weaker than FL118.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	52-57	baculoviral IAP repeat containing 3	Homo sapiens	267-272
26692923-6	2015	Lastly, in contrast to both SN-38 (active metabolite of irinotecan) and topotecan are substrates of the efflux pump proteins P-gp/MDR1 and ABCG2/BCRP, FL118 is not a substrate of P-gp and ABCG2.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	151-156	ATP binding cassette subfamily B member 1	Homo sapiens	130-134
26692923-6	2015	Lastly, in contrast to both SN-38 (active metabolite of irinotecan) and topotecan are substrates of the efflux pump proteins P-gp/MDR1 and ABCG2/BCRP, FL118 is not a substrate of P-gp and ABCG2.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	151-156	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	139-144
26692923-9	2015	Given that both P-gp and ABCG2 express in SW620 and HCT-8 cells and FL118 is not a substrate for P-gp and ABCG2, this suggests that FL118 appears to bypass multiple efflux pump protein-induced resistance, which may contribute to FL118 overcoming irinotecan and topotecan resistance in vivo.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	132-137	phosphoglycolate phosphatase	Homo sapiens	16-20
26692923-9	2015	Given that both P-gp and ABCG2 express in SW620 and HCT-8 cells and FL118 is not a substrate for P-gp and ABCG2, this suggests that FL118 appears to bypass multiple efflux pump protein-induced resistance, which may contribute to FL118 overcoming irinotecan and topotecan resistance in vivo.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	132-137	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	25-30
25928015-8	2015	Lastly, we investigated a series of FL118 analogues with B-ring substitutions for ABCG2 sensitivity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	82-87
25928015-9	2015	RESULTS: Both pharmacological inhibition and genetic modulation of ABCG2 demonstrated that, in contrast to SN-38, FL118 was able to bypass ABCG2-mediated drug resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	114-119	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	67-72
25928015-0	2015	FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	170-175
25928015-9	2015	RESULTS: Both pharmacological inhibition and genetic modulation of ABCG2 demonstrated that, in contrast to SN-38, FL118 was able to bypass ABCG2-mediated drug resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	114-119	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	139-144
25928015-4	2015	In this study, we sought to investigate the potency of FL118 versus irinotecan or its active metabolite, SN-38, in both in vitro and in vivo models of human cancer with high ABCG2 activity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	55-60	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	174-179
25928015-11	2015	Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	25-30	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	90-95
25928015-11	2015	Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	25-30	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	168-173
25928015-11	2015	Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	136-141	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	90-95
25928015-11	2015	Lastly, we observed that FL118 analogues with polar substitutions had higher affinity for ABCG2, suggesting that the nonpolar nature of FL118 plays a role in bypassing ABCG2-mediated resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	136-141	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	168-173
25928015-12	2015	CONCLUSIONS: Our results suggest that in contrast to SN-38 and topotecan, FL118 is a poor substrate for ABCG2 and can effectively overcome ABCG2-mediated drug resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	74-79	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	104-109
25928015-12	2015	CONCLUSIONS: Our results suggest that in contrast to SN-38 and topotecan, FL118 is a poor substrate for ABCG2 and can effectively overcome ABCG2-mediated drug resistance.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	74-79	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	139-144
25928015-13	2015	Our findings expand the uniqueness of FL118 and support continued development of FL118 as an attractive therapeutic option for patients with drug-refractory cancers resulting from high expression of ABCG2.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	81-86	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	199-204
23029106-0	2012	A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	23-28	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	65-70
25512388-0	2014	FL118 induces p53-dependent senescence in colorectal cancer cells by promoting degradation of MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	tumor protein p53	Homo sapiens	14-17
25512388-0	2014	FL118 induces p53-dependent senescence in colorectal cancer cells by promoting degradation of MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MDM4 regulator of p53	Homo sapiens	94-98
25512388-4	2014	Here, we report that FL118 activates tumor suppressor p53 as a novel MOA in p53 wild-type cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	21-26	tumor protein p53	Homo sapiens	54-57
25512388-4	2014	Here, we report that FL118 activates tumor suppressor p53 as a novel MOA in p53 wild-type cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	21-26	tumor protein p53	Homo sapiens	76-79
25512388-6	2014	FL118 inhibits p53 polyubiquitination and monoubiquitination by Mdm2-MdmX E3 complex in cells and in cell-free systems.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	tumor protein p53	Homo sapiens	15-18
25512388-6	2014	FL118 inhibits p53 polyubiquitination and monoubiquitination by Mdm2-MdmX E3 complex in cells and in cell-free systems.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MDM2 proto-oncogene	Homo sapiens	64-68
25512388-6	2014	FL118 inhibits p53 polyubiquitination and monoubiquitination by Mdm2-MdmX E3 complex in cells and in cell-free systems.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MDM4 regulator of p53	Homo sapiens	69-73
25512388-7	2014	In contrast, FL118 stimulates Mdm2-mediated MdmX ubiquitination.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	13-18	MDM2 proto-oncogene	Homo sapiens	30-34
25512388-7	2014	In contrast, FL118 stimulates Mdm2-mediated MdmX ubiquitination.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	13-18	MDM4 regulator of p53	Homo sapiens	44-48
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM2 proto-oncogene	Homo sapiens	61-65
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	tumor protein p53	Homo sapiens	66-69
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM2 proto-oncogene	Homo sapiens	108-112
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM4 regulator of p53	Homo sapiens	113-117
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM2 proto-oncogene	Homo sapiens	108-112
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM4 regulator of p53	Homo sapiens	185-189
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	tumor protein p53	Homo sapiens	206-209
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM4 regulator of p53	Homo sapiens	185-189
25512388-8	2014	Coimmunoprecipitation revealed that FL118 slightly decreases Mdm2-p53 interactions and moderately increases Mdm2-MdmX interactions, suggesting a change of targeting specificity of Mdm2-MdmX E3 complex from p53 to MdmX, resulting in accelerated MdmX degradation.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	36-41	MDM4 regulator of p53	Homo sapiens	185-189
25512388-10	2014	Activation of the p53 pathway by FL118 induces p53-dependent senescence in colorectal cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	33-38	tumor protein p53	Homo sapiens	18-21
25512388-10	2014	Activation of the p53 pathway by FL118 induces p53-dependent senescence in colorectal cancer cells.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	33-38	tumor protein p53	Homo sapiens	47-50
25512388-11	2014	However, in the absence of p53 or in the presence of MdmX overexpression, FL118 promotes p53-independent apoptosis.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	74-79	MDM4 regulator of p53	Homo sapiens	53-57
25512388-11	2014	However, in the absence of p53 or in the presence of MdmX overexpression, FL118 promotes p53-independent apoptosis.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	74-79	tumor protein p53	Homo sapiens	89-92
25512388-13	2014	This study identifies a potential application of FL118 as an MdmX inhibitor for targeted therapies.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	49-54	MDM4 regulator of p53	Homo sapiens	61-65
24959385-9	2014	FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	X-linked inhibitor of apoptosis	Homo sapiens	79-83
24959385-9	2014	FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	baculoviral IAP repeat containing 3	Homo sapiens	85-90
24959385-9	2014	FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	182-187
24959385-9	2014	FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	BCL2 apoptosis regulator	Homo sapiens	195-200
24959385-9	2014	FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	BCL2 associated X, apoptosis regulator	Homo sapiens	251-254
24959385-9	2014	FL118 was found to not only inhibit multiple antiapoptotic proteins (survivin, XIAP, cIAP2) in the inhibitor of apoptosis (IAP) family, but to also inhibit the antiapoptotic protein Mcl-1 in the Bcl-2 family, while inducing the pro-apoptotic proteins Bax and Bim expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	BCL2 like 11	Homo sapiens	259-262
24959385-10	2014	Importantly, inhibition of these target genes and of tumor growth by FL118 is independent of p53 status (wild type, mutant or null), although mechanisms of action may be distinct among cells with different p53 status.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	69-74	tumor protein p53	Homo sapiens	206-209
24959385-11	2014	Therefore, FL118 may effectively control cancer that loses functional p53, in which most DNA damage drugs (if not all) show a marked lack of efficiency.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	11-16	tumor protein p53	Homo sapiens	70-73
23573360-1	2013	route-compatible formulation of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, improves FL118 antitumor efficacy and therapeutic index (TI).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	32-37	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	51-56
23573360-1	2013	route-compatible formulation of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, improves FL118 antitumor efficacy and therapeutic index (TI).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	32-37	X-linked inhibitor of apoptosis	Homo sapiens	58-62
23573360-1	2013	route-compatible formulation of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, improves FL118 antitumor efficacy and therapeutic index (TI).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	32-37	baculoviral IAP repeat containing 3	Homo sapiens	68-73
23573360-3	2013	FL118 selectively inhibits the expression of four major cancer survival-associated gene products (survivin, Mcl-1, XIAP, and cIAP2) and shows promising antitumor activity in animal models of human cancers when administered using a weekly x 4 schedule (Ling et al., PLOS ONE.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	108-113
23573360-3	2013	FL118 selectively inhibits the expression of four major cancer survival-associated gene products (survivin, Mcl-1, XIAP, and cIAP2) and shows promising antitumor activity in animal models of human cancers when administered using a weekly x 4 schedule (Ling et al., PLOS ONE.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	X-linked inhibitor of apoptosis	Homo sapiens	115-119
23573360-3	2013	FL118 selectively inhibits the expression of four major cancer survival-associated gene products (survivin, Mcl-1, XIAP, and cIAP2) and shows promising antitumor activity in animal models of human cancers when administered using a weekly x 4 schedule (Ling et al., PLOS ONE.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	baculoviral IAP repeat containing 3	Homo sapiens	125-130
24329001-0	2014	Antitumor activity of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, is highly dependent on its primary structure and steric configuration.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	22-27	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	41-46
24329001-0	2014	Antitumor activity of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, is highly dependent on its primary structure and steric configuration.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	22-27	X-linked inhibitor of apoptosis	Homo sapiens	48-52
24329001-0	2014	Antitumor activity of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, is highly dependent on its primary structure and steric configuration.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	22-27	baculoviral IAP repeat containing 3	Homo sapiens	58-63
24329001-2	2014	FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., PLoS One 2012, 7, e45571).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	115-120
24329001-2	2014	FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., PLoS One 2012, 7, e45571).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	X-linked inhibitor of apoptosis	Homo sapiens	122-126
24329001-2	2014	FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., PLoS One 2012, 7, e45571).	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	baculoviral IAP repeat containing 3	Homo sapiens	128-133
24329001-5	2014	Consistently, FL118 proved much more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both in vitro and in vivo, compared to FL113.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	14-19	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	89-94
24329001-5	2014	Consistently, FL118 proved much more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both in vitro and in vivo, compared to FL113.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	14-19	baculoviral IAP repeat containing 3	Homo sapiens	100-105
24329001-6	2014	Additionally, Tet-on controlled induction of survivin or forced expression of Mcl-1 protects cancer cells from FL118-mediated growth inhibition and cell death.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	111-116	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	78-83
23029106-8	2012	Although the survivin promoter-reporter system was used for the identification of FL118, our studies revealed that FL118 not only inhibits survivin expression but also selectively and independently inhibits three additional cancer-associated survival genes (Mcl-1, XIAP and cIAP2) in a p53 status-independent manner, while showing no inhibitory effects on control genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	115-120	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	258-263
23029106-8	2012	Although the survivin promoter-reporter system was used for the identification of FL118, our studies revealed that FL118 not only inhibits survivin expression but also selectively and independently inhibits three additional cancer-associated survival genes (Mcl-1, XIAP and cIAP2) in a p53 status-independent manner, while showing no inhibitory effects on control genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	115-120	X-linked inhibitor of apoptosis	Homo sapiens	265-269
23029106-8	2012	Although the survivin promoter-reporter system was used for the identification of FL118, our studies revealed that FL118 not only inhibits survivin expression but also selectively and independently inhibits three additional cancer-associated survival genes (Mcl-1, XIAP and cIAP2) in a p53 status-independent manner, while showing no inhibitory effects on control genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	115-120	baculoviral IAP repeat containing 3	Homo sapiens	274-279
23029106-8	2012	Although the survivin promoter-reporter system was used for the identification of FL118, our studies revealed that FL118 not only inhibits survivin expression but also selectively and independently inhibits three additional cancer-associated survival genes (Mcl-1, XIAP and cIAP2) in a p53 status-independent manner, while showing no inhibitory effects on control genes.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	115-120	tumor protein p53	Homo sapiens	286-289
23029106-0	2012	A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	23-28	X-linked inhibitor of apoptosis	Homo sapiens	72-76
23029106-0	2012	A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	23-28	baculoviral IAP repeat containing 3	Homo sapiens	81-86
23029106-0	2012	A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	23-28	tumor protein p53	Homo sapiens	92-95
23029106-6	2012	However, while the inhibition of DNA topoisomerase 1 activity by FL118 was no better than the active form of irinotecan, SN-38 at 1 microM, FL118 effectively inhibited cancer cell growth at less than nM levels in a p53 status-independent manner.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	65-70	DNA topoisomerase I	Homo sapiens	33-52
23029106-7	2012	Moreover, FL118 selectively inhibited survivin promoter activity and gene expression also in a p53 status-independent manner.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	10-15	tumor protein p53	Homo sapiens	95-98
34377229-0	2021	Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	79-84	KRAS proto-oncogene, GTPase	Homo sapiens	0-4
34377229-0	2021	Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	79-84	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	117-122
34377229-5	2021	This finding suggests that both KrasG12V and KrasG12D are required for showing higher FL118 efficacy, while the presence of KrasG13D could somehow decrease FL118 efficacy under the defined p53/APC genetic status.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	156-161	tumor protein p53	Homo sapiens	189-192
34377229-0	2021	Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	79-84	X-linked inhibitor of apoptosis	Homo sapiens	124-128
34377229-5	2021	This finding suggests that both KrasG12V and KrasG12D are required for showing higher FL118 efficacy, while the presence of KrasG13D could somehow decrease FL118 efficacy under the defined p53/APC genetic status.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	156-161	APC regulator of WNT signaling pathway	Homo sapiens	193-196
34377229-10	2021	These findings would be useful for predicting FL118 sensitivity to patients" CRC tumors with the defined Kras mutation subtypes under the defined p53/APC genetic status.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	46-51	KRAS proto-oncogene, GTPase	Homo sapiens	105-109
34377229-0	2021	Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	79-84	baculoviral IAP repeat containing 3	Homo sapiens	130-135
34377229-10	2021	These findings would be useful for predicting FL118 sensitivity to patients" CRC tumors with the defined Kras mutation subtypes under the defined p53/APC genetic status.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	46-51	tumor protein p53	Homo sapiens	146-149
34377229-0	2021	Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	79-84	MDM4 regulator of p53	Homo sapiens	140-144
34377229-10	2021	These findings would be useful for predicting FL118 sensitivity to patients" CRC tumors with the defined Kras mutation subtypes under the defined p53/APC genetic status.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	46-51	APC regulator of WNT signaling pathway	Homo sapiens	150-153
34377229-3	2021	Here, we report that while FL118 (a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX) exhibits high efficacy to kill CRC cells and eliminate CRC tumors, CRC cells/tumors with different Kras mutation subtypes in the defined p53/APC genetic statuses exhibit different sensitivity to FL118 treatment.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	27-32	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	65-70
34377229-3	2021	Here, we report that while FL118 (a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX) exhibits high efficacy to kill CRC cells and eliminate CRC tumors, CRC cells/tumors with different Kras mutation subtypes in the defined p53/APC genetic statuses exhibit different sensitivity to FL118 treatment.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	27-32	X-linked inhibitor of apoptosis	Homo sapiens	72-76
34377229-3	2021	Here, we report that while FL118 (a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX) exhibits high efficacy to kill CRC cells and eliminate CRC tumors, CRC cells/tumors with different Kras mutation subtypes in the defined p53/APC genetic statuses exhibit different sensitivity to FL118 treatment.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	27-32	baculoviral IAP repeat containing 3	Homo sapiens	78-83
34377229-3	2021	Here, we report that while FL118 (a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX) exhibits high efficacy to kill CRC cells and eliminate CRC tumors, CRC cells/tumors with different Kras mutation subtypes in the defined p53/APC genetic statuses exhibit different sensitivity to FL118 treatment.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	27-32	MDM4 regulator of p53	Homo sapiens	88-92
35604033-0	2022	FL118, acting as a "molecular glue degrader", binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	DEAD-box helicase 5	Homo sapiens	101-105
35604033-0	2022	FL118, acting as a "molecular glue degrader", binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	DEAD-box helicase 5	Homo sapiens	107-110
35604033-0	2022	FL118, acting as a "molecular glue degrader", binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	123-128
35604033-0	2022	FL118, acting as a "molecular glue degrader", binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	KRAS proto-oncogene, GTPase	Homo sapiens	150-154
35604033-5	2022	METHODS: FL118 affinity purification, mass spectrometry, Nanosep centrifugal device and isothermal titration calorimetry were used for identifying and confirming FL118 binding to DDX5/p68 and its binding affinity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	162-167	DEAD-box helicase 5	Homo sapiens	179-183
35604033-5	2022	METHODS: FL118 affinity purification, mass spectrometry, Nanosep centrifugal device and isothermal titration calorimetry were used for identifying and confirming FL118 binding to DDX5/p68 and its binding affinity.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	162-167	DEAD-box helicase 5	Homo sapiens	184-187
35604033-9	2022	RESULTS: We discovered that FL118 strongly binds to dephosphorylates and degrades the DDX5 oncoprotein via the proteasome degradation pathway without decreasing DDX5 mRNA.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	28-33	DEAD-box helicase 5	Homo sapiens	86-90
35604033-13	2022	Our human tumour animal model studies further indicated that FL118 exhibits high efficacy to eliminate human PDAC and CRC tumours that have a high expression of DDX5, while FL118 exhibits less effectiveness in PDAC and CRC tumours with low DDX5 expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	61-66	DEAD-box helicase 5	Homo sapiens	161-165
35604033-13	2022	Our human tumour animal model studies further indicated that FL118 exhibits high efficacy to eliminate human PDAC and CRC tumours that have a high expression of DDX5, while FL118 exhibits less effectiveness in PDAC and CRC tumours with low DDX5 expression.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	173-178	DEAD-box helicase 5	Homo sapiens	240-244
35604033-14	2022	CONCLUSION: DDX5 is a bona fide FL118 direct target and can act as a biomarker for predicting PDAC and CRC tumour sensitivity to FL118.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	32-37	DEAD-box helicase 5	Homo sapiens	12-16
35604033-14	2022	CONCLUSION: DDX5 is a bona fide FL118 direct target and can act as a biomarker for predicting PDAC and CRC tumour sensitivity to FL118.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	129-134	DEAD-box helicase 5	Homo sapiens	12-16
35604033-16	2022	FL118 may act as a "molecular glue degrader" to directly glue DDX5 and ubiquitination regulators together to degrade DDX5.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	DEAD-box helicase 5	Homo sapiens	62-66
35604033-16	2022	FL118 may act as a "molecular glue degrader" to directly glue DDX5 and ubiquitination regulators together to degrade DDX5.	7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione	0-5	DEAD-box helicase 5	Homo sapiens	117-121