246513-41-7Relevant 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
-
Paragraph 0183; 0185; 0186, (2018/12/01)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
Diaza tropolium ion carbazole IDO inhibitor and application thereof
-
Paragraph 0034; 0035; 0036; 0037, (2018/12/05)
The invention belongs to the field of chemical medicine and particularly relates to a diaza tropolium ion carbazole IDO inhibitor or the pharmaceutically acceptable salt thereof, pharmaceutical compositions containing the compounds, and application of the
FUSED TETRACYCLIC OR FUSED PENTACYCLIC DIHYDRO DIAZEPINO CARBAZOLONE AS PARP INHIBITOR
-
Paragraph 0121, (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
-
Paragraph 0222; 0223, (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
-
Page/Page column 40, (2013/07/19)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
Substituted tricyclics
-
, (2008/06/13)
A class of novel tricyclics is disclosed together with the use of such compounds for inhibiting sPLA2mediated release of fatty acids for treatment of conditions such as septic shock.
Substituted carbazoles, process for their preparation and their use as sPLA2 inhibitors
-
, (2008/06/13)
Novel tricyclics are disclosed together with the use of such compounds for inhibiting SPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.
