RUSKI-201 dihydrochloride

RUSKI-201 dihydrochloride is a potent and specific Hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 0.20 μM. RUSKI-201 dihydrochloride is able to block Hh signaling from Shh overexpressing cells and inhibits Hh palmitoylation. RUSKI-201 dihydrochloride is potential Hhat chemical probe in cells and can used in studies of Hhat catalytic function[1].

Research Areas >> Cancer

Signaling Pathways >> Stem Cell/Wnt >> Hedgehog

RUSKI-201 (0.5-25 μM; 48 hours) has no effect on cell viability at concentrations >25 μM in Shh-Light2 cells derived from NIH3T3 cells stably transfected with a Gli-responsive firefly luciferase HEK-293 cells stably overexpressing Shh[1]. RUSKI-201 inhibits signaling in H520, Panc-1, and MCF-7 coculture with Shh-Light2 cells (IC50=4.8±0.60 μM, 7.8±1.3 μM, and 8.5±0.65 μM, respectively)[1]RUSKI-201 (0.01-10 μM; 24 hours) induces a selective inhibition of Shh palmitoylation and does not affect global palmitoylation levels in HEK-293 Shh+ cells treated with RUSKI-201 followed by YnPal and functionalized with AzTB[1]. Western Blot Analysis[1] Cell Line: HEK-293 Shh+ cells Concentration: 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM Incubation Time: 24 hours Result: Decreased YnPal-Shh expression without α-Shh change; Capable of blocking Hh signaling from Shh overexpressing cells.

[1]. Ursula R Rodgers, et al. Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells. ACS Chem Biol. 2016 Dec 16;11(12):3256-3262.