NMS-E973

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NMS-E973 是一种有效的选择性 Hsp90 抑制剂，Hsp90 结合的 DC50 <10 nM，对 52 种不同的蛋白激酶没有活性。

NMS-E973 is a novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). NMS-E973 displays significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile. The efficacy profile of NMS-E973 suggests a potential for development in different clinical settings, including tumors that have become resistant to molecular targeted agents, particularly in cases of tumors which reside beyond the blood-brain barrier (BBB).

NMS-E973 inhibits cancer cell proliferation. NMS-E973 shows a widespread antiproliferative activity, with an average IC50 of 1.6 μM and 15 cell lines with an IC50 <100 nM. Cell Proliferation Assay Cell Line:Carcinoma breast DU-4475, EVSA-T, CAL-51, HCC1954, BT-474, HCC1419, HDQ-P1 cells; Leukemia MV-4-11 and MOLM-13 cells; Melanoma A-375 cellsConcentration:Incubation Time:24, 48, 72 hours Result:IC50s of 13, 16, 56, 61, 73, 76, and 89 nM for DU-4475, EVSA-T, CAL-51, HCC1954, BT-474, HCC1419, HDQ-P1 cells, respectively.IC50s of 29 and 35 nM for MV-4-11, MOLM-13 cells, respectively.The IC50 of 133 nM for A-375 cell.

NMS-E973 (60 mg/kg; i.v.) inhibits the growth of A375 tumors subcutaneously or intracranially implanted in mice. NMS-E973 exhibits moderate elimination half-lives (5.55±1.07 h) due to high plasma clearance (39.9±1.70 mL/min/kg) combined with large volumes of distribution (5.83±3.18 L/kg) following intravenous administration (10 mg/kg) in mice. Animal Model:Balb/c male nude mice (aged 6 to 8 weeks) xenografted with the A375 tumors Dosage:60 mg/kg Administration:Administered twice daily i.v. according to 2 schedules: (i) every other day for 12 days and (ii) 3 days on/1 day off/3 days on (3-1-3, one cycle). Result:Both schedules resulted in tumor shrinkage and TGI of 74% and 89%, respectively.

NMS-E973 | NMSE973

Others

Platelet aggregation

HSP90

Cancer

——

1253584-84-7

454.43

C22H22N4O7

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (110.03 mM)

CN1CCC(CC1)NC(=O)C2=C/C(=C\3/C(=CC(=O)C=C3OC4=CC=C(C=C4)[N+](=O)[O-])O)/ON2

5-[2,4-Dihydroxy-6-(4-nitrophenoxy)phenyl]-N-(1-methyl-4-piperidinyl)-3-isoxazolecarboxamide

(-20℃)

With Ice Pack

≥ 2 years