JG-98

JG-98 is an allosteric heat shock protein 70 (Hsp70) inhibitor with anti-cancer activities, which disrupts Hsp70 interaction with a co-chaperone Bag3 and affects signaling pathways important for cancer development[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HSP

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

Heat shock protein 70[1]

JG-98 inhibits the breast cancer cell lines MDA-MB-231 and MCF-7 with EC50 values of 0.4 and 0.7 μM, respectively[1]. JG-98 (30 nM-30 μM; 72 hours) has antiproliferative activity across a range of cell lines[2]. JG-98 (10 μM; 48 hours) activates both apoptotic mediators (cleavage of caspase-3 and PARP) in MDA-MB-231 cells[1]. Cell Proliferation Assay[2] Cell Line: MCF-7, MDA-MB-231, A375, MeWo, HeLa, HT-29, SKOV3, Jurkat, mouse embryonic fibroblasts (MEF), MM1.R, INA6, RPMI-8226, JJN-3, U266, NCI-H929, L363, MM1.S, KMS11, LP-1, AMO-1, OPM1, OPM2 cells Concentration: 30 nM-30 μM Incubation Time: 72 hours Result: Active against all of the lines tested, and the EC50s were variable (between ~0.3 μM and 4 μM). Normal MEFs and OPM1 and OPM2 were relatively less sensitive. Western Blot Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 10 μM Incubation Time: 48 hours Result: Incudes cleavage of caspase 3 and PARP.

JG-98 (3 mg/kg; i.p.; on days 0, 2, and 4) is active against MCF7 cells in xenograft models[2]. Animal Model: 6-week-old NCR mice (xenografts of MCF7 cells)[2] Dosage: 3 mg/kg Administration: Intraperitoneal injection; on days 0, 2, and 4 Result: Limited tumor growth until day 6, but tumors appeared to resume growing following the end of drug administration.

[1]. Li X, et al. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013 Nov 14;4(11).

[2]. Li X, et al. Validation of the Hsp70-Bag3 protein-protein interaction as a potential therapeutic target in cancer. Mol Cancer Ther. 2015 Mar;14(3):642-8.

[3]. Yaglom JA, et al. Cancer cell responses to Hsp70 inhibitor JG-98: Comparison with Hsp90 inhibitors and findingsynergistic drug combinations. Sci Rep. 2018 Feb 14;8(1):3010.