NMS-E973

NMS-E973 is a potent and selective inhibitor of HSP90. NMS-E973 binds to the ATP binding site of Hsp90α with a DC50 of <10 nM. NMS-E973 is able to cross the blood-brain barrier (BBB). Antitumor efficacy[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HSP

Signaling Pathways >> Cell Cycle/DNA Damage >> HSP

HSP90α:10 nM (DC50)

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[1]. Cell Proliferation Assay[1] 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 cells Concentration: 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[1]. 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[1]. Animal Model: Balb/c male nude mice (aged 6 to 8 weeks) xenografted with the A375 tumors[1] 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.

[1]. Gianpaolo Fogliatto, et al. NMS-E973, a novel synthetic inhibitor of Hsp90 with activity against multiple models of drug resistance to targeted agents, including intracranial metastases. Clin Cancer Res. 2013 Jul 1;19(13):3520-32.