Most of the compounds have physiologically active properties, and their biological properties are often attributed to the heteroatoms contained in their molecules, and most of these heteroatoms also appear in cyclic structures. A Journal, Article, Journal of Medicinal Chemistry called Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development, Author is 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, which mentions a compound: 17739-45-6, SMILESS is BrCCOC1CCCCO1, Molecular C7H13BrO2, HPLC of Formula: 17739-45-6.
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 enzymic 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, resp. 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 clin. trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.
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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem