1446261-45-5Relevant academic research and scientific papers
Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development
Wang, Hexiang,Ren, Bo,Liu, Ye,Jiang, Beibei,Guo, Yin,Wei, Min,Luo, Lusong,Kuang, Xianzhao,Qiu, Ming,Lv, Lei,Xu, Hong,Qi, Ruipeng,Yan, Huibin,Xu, Dexu,Wang, Zhiwei,Huo, Chang-Xin,Zhu, Yutong,Zhao, Yuan,Wu, Yiyuan,Qin, Zhen,Su, Dan,Tang, Tristin,Wang, Fan,Sun, Xuebing,Feng, Yingcai,Peng, Hao,Wang, Xing,Gao, Yajuan,Liu, Yong,Gong, Wenfeng,Yu, Fenglong,Liu, Xuesong,Wang, Lai,Zhou, Changyou
, p. 15541 - 15563 (2020/12/22)
Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC50 of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC50 = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.
FUSED TETRA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARP INHIBITORS
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Paragraph 0192; 0194; 0195, (2018/12/01)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
FUSED TETRACYCLIC OR FUSED PENTACYCLIC DIHYDRO DIAZEPINO CARBAZOLONE AS PARP INHIBITOR
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Paragraph 0126, (2017/06/24)
PROBLEM TO BE SOLVED: To provide a specific fused tetracyclic or fused pentacyclic compound, and its salt, its composition, and a method for use thereof. SOLUTION: The present invention provides a compound represented by formula (I), its stereoisomer and pharmaceutically acceptable salt, where RN is H, alkyl or the like; X is C, N, O or S; m and n independently represent an integer of 0-3; t is an integer of 0-3; R1-R8 are H, an alkyl group, an alkenyl group, a heterocyclyl group and the like. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
FUSED TETRA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARP INHIBITORS
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Paragraph 0230; 0231, (2015/07/02)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
FUSED TETRA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARP INHIBITORS
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Page/Page column 44; 45, (2013/07/19)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
