RU-SKI 43 --- Hhat Inhibitor

RU-SKI 43 is the first potent and specific small molecule inhibitor of Hedgehog acyltransferase (Hhat), and directly inhibits palmitoylation of the Shh ligand. It was discovered by a high-throughput screen using a peptide-based assay to monitor Hhat-mediated Shh palmitoylation (IC50 ~0.85 μM) . In vitro using purified Hhat and ShhN to analyze the kinetics of compound’s inhibition of ShhN palmitoylation, RU-SKI 43 behaved 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-palmitoyl CoA. In cells, RU-SKI 43 specifically blocks Shh palmitoylation and inhibits autocrine and paracrine Shh signaling. Hhat inhibitor could offer a new treatment modality for cancers characterized by Shh overexpression and extremely poor prognoses

Product information

CAS Number: 1043797-53-0

Molecular Weight: 386.55

Formula: C22H30N2O2S

Chemical Name: 2-((2-methylbutyl)amino)-1-(4-((m-tolyloxy)methyl)-3a, 4, 7, 7a-tetrahydrothieno[3, 2- c]pyridin-5(6H)-yl)ethanone

Smiles: CC1C=CC=C(C=1)OCC1C2C=CSC=2CCN1C(=O)CNCC(C)CC

InChiKey: AEENEMOEBJOKGN-UHFFFAOYSA-N

InChi: InChI=1S/C22H30N2O2S/c1-4-16(2)13-23-14-22(25)24-10-8-21-19(9-11-27-21)20(24)15-26-18-7-5-6-17(3)12-18/h5-7,9,11-12,16,20,23H,4,8,10,13-15H2,1-3H3

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

RU-SKI 43 was used at 10-20 µM final concentration in vitro and in cellular assays.

References:

1. Petrova E, et al. Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling. (2013) Nat Chem Biol. 9(4):247-9.
2. Petrova E, et al. Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma. (2014) Oncogene. In press.

Products are for research use only. Not for human use.

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