SM253

SM253 is an Hsp90 inhibitor that inhibits Hsp90-dependent protein folding. SM253 blocks chaperone function by binding to the N-middle linker region and the C-terminal M domain, reducing co-chaperone and client protein binding and activation. SM253 induces cancer cell apoptosis, activates caspase 3/7, causes cell cycle arrest and reduces cell proliferation, while decreasing Hsp90 client proteins such as AR, FKBP51, PSA, Cdk4, AKT, ERK, and p23, and reducing Hsp27/Hsp70 expression without inducing heat shock proteins. SM253 causes dose-dependent fibronectin loss in cells expressing LRP1. SM253 can be used for research on colon cancer, pancreatic cancer, and prostate cancer^[1][2][3]. In Vitro:SM253 (5 μM; 2 h) inhibits hsp90-mediated protein folding in rabbit reticulocyte lysate, reducing luciferase activity by 42%^[1].
SM253 (5-50 μM; 24 h) reduces HSR proteins by approximately 2-4 fold and depletes hsp27 in HCT-116 cells without inducing a heat shock response^[1].
SM253 (2-25 μM; 16 h) induces dose-dependent fibronectin loss in LRP1-expressing MEF-1 cells but not in LRP1-deficient PEA-13 cells^[3].
The IC₅₀ values of SM253 in HCT-116 and MiaPaCa-2 cells are 5.0 μM and 5.5 μM, respectively^[1].
SM253 (2500-10000 nM; 4 days) inhibits the growth of LNCaP, 22Rv1, and PC-3 prostate cancer cells with an IC₅₀ of approximately 5 µM and reduces the proliferation of PC-3 cells^[2].
SM253 (5-10 μM; 48 h) reduces Hsp27/Hsp70 and selected Hsp90 client/co-chaperone proteins in LNCaP, 22Rv1, and PC-3 prostate cancer cells without inducing a heat shock response^[2].
SM253 (50 μM; 24 h) induces apoptosis in HCT-116 and MiaPaCa-2 cells^[1].
SM253 (24 h) increases caspase 3/7 activity 4-fold in HCT-116 and MiaPaCa-2 cells^[1].
SM253 (5-10 μM; 48 h) induces caspase-dependent apoptosis in prostate cancer cell lines, and this cell death is blocked by the pan-caspase inhibitor Z-VAD-fmk (HY-16658B)^[2].
SM253 (24 h) arrests HCT-116 and MiaPaCa-2 cells in the G0/G1 phase^[1].