PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 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 25512388-4 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 25512388-8 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 tumor protein p53 Homo sapiens 206-209 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 tumor protein p53 Homo sapiens 89-92 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 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 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 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 34377229-10 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