RU-SKI 43

Research use only, not for human use.

A small molecule inhibitor of Hhat (Hedgehog acyltransferase) with IC50 of 0.85 uM.

A small molecule inhibitor of Hhat (Hedgehog acyltransferase) with IC50 of 0.85 uM; specific to Shh palmitoylation and no effect for palmitoylation of H-Ras, Fyn and myristoylation of c-Src; reduces pancreatic cancer cell proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling, inhibits two key proliferative pathways regulated by Akt and mTOR.

RU-SKI 43 (10 μM; for 6 days) strongly decreases cell proliferation (83% in AsPC-1 cells) in AsPC-1 and Panc-1 cells. RU-SKI 43 (10 or 20 μM; 5 hours) causes dose-dependent inhibition of Shh palmitoylation following only 5 hours. RU-SKI 43 (10 μM; for 72 hours) causes a 40% decrease in Gli-1 levels in AsPC-1 cells. RU-SKI 43 (10μM; 48 hours) results in decreased phosphorylation (47-67%) of four proteins in the Akt pathway, including Akt (phosphorylation at both Thr307 and Ser473), PRAS40, Bad and GSK-3β. RU-SKI 43 treatment also decreases phosphorylation of mTOR and S6, members of the mTOR signaling pathway. RU-SKI 43 behaves as an uncompetitive inhibitor (Ki=7.4 μM) with respect to Shh, and as a noncompetitive inhibitor (Ki=6.9 μM) with respect to 125I-iodo-palmitoylCoA. They are for reference only.RU-SKI 43 :Cell Proliferation AssayCell Line:AsPC-1 and Panc-1 pancreatic cancer cells Concentration:10 μM Incubation Time:For 6 days (drugs were replenished every 48 hours)Result:Strongly decreased cell proliferation (83% in AsPC-1 cells).

RU-SKI 43 has a t1/2 of 17 min in mouse plasma after IV administration.

RUSKI-43

GPCR/G Protein

Hedgehog (Hh)

Hedgehog (Hh)

Cancer

——

1043797-53-0

386.5508

C22H30N2O2S

>98% (HPLC)

10 mM in DMSO

CCC(C)CNCC(=O)N1CCC2=C(C1COC3=CC=CC(=C3)C)C=CS2

Ethanone, 1-[6,7-dihydro-4-[(3-methylphenoxy)methyl]thieno[3,2-c]pyridin-5(4H)-yl]-2-[(2-methylbutyl)amino]-

(-20℃)

With Ice Pack

≥ 2 years