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VER-82576

CAS No. : 847559-80-2

MCE 国际站：VER-82576

产品活性：VER-82576 (NVP-BEP800) 是一种有效的，可口服的，选择性的 Hsp90 抑制剂，对 Hsp90β 的 IC₅₀ 值为 58 nM；VER-82576 同时可较弱地抑制 Grp94 和 Trap-1 的活性，IC₅₀ 值分别为 4.1 和 5.5 μM。

研究领域：Cell Cycle/DNA Damage  |  Metabolic Enzyme/Protease

作用靶点：HSP

In Vitro: VER-82576 (NVP-BEP800) is a potent and selective Hsp90 inhibitor, with an IC₅₀ of 58 nM for Hsp90β and is >70-fold selective against Grp94 and Trap-1, with IC₅₀s of 4.1 ± 1.1 and 5.5 ± 0.48 μM. VER-82576 potently inhibits the proliferation of tumor cells, with GI₅₀s ranging from 38 nM in A375 cells to 1050 nM in PC3 cells, with an average GI₅₀ of 245 nM. VER-82576 (250-1250 nM) depletes client proteins in human cancer cell lines in vitro. VER-82576 (NVP-BEP800; 200 nM) shows no significant effect on the ionizing radiation (IR) dose-response curves of A549 cells, and is less toxic to SNB19 cells. VER-82576 in combination with IR results in more severe DNA damage in both A549 and SNB19 cell lines than each treatment alone and also protracts the kinetics of DNA damage repair in SNB19 cells. VER-82576 (NVP-BEP800; 0.05, 0.1 or 0.2 μM) dose-dependently decreases the viability and induces apoptosis of glioblastoma cells. VER-82576 (0.2 μM) suppresses the expression of IKKβ protein but does not alter the levels of IKKβ mRNA in T98G cells. VER-82576 (0.2 μM) suppresses the expression of heat shock protein 70.

In Vivo: VER-82576 (NVP-BEP800; 15 or 30 mg/kg, p.o.) shows antitumor activities in A375 cancer xenografts and BT-474 xenograft-bearing mice.

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