BibTex format
@article{Rodgers:2016:10.1021/acschembio.6b00896,
author = {Rodgers, U and Lanyon-Hogg, T and Masumoto, N and Ritzefeld, M and Burke, R and Blagg, J and Magee, A and Tate, E},
doi = {10.1021/acschembio.6b00896},
journal = {ACS Chemical Biology},
pages = {3256--3262},
title = {Characterization of hedgehog acyltransferase inhibitors identifies a small molecule probe for hedgehog signaling by cancer cells},
url = {http://dx.doi.org/10.1021/acschembio.6b00896},
volume = {11},
year = {2016}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, raising interest in Hhat as a novel drug target. A recently identified series of dihydrothienopyridines has been proposed to function via this mode of action; however, the lead compound in this series (RUSKI-43) was subsequently shown to possess cytotoxic activity unrelated to canonical Shh signaling. To identify a selective chemical probe for cellular studies, we profiled three RUSKI compounds in orthogonal cell-based assays. We found that RUSKI-43 exhibits off-target cytotoxicity, masking its effect on Hhat-dependent signaling, hence results obtained with this compound in cells should be treated with caution. In contrast, RUSKI-201 showed no off-target cytotoxicity, and quantitative whole-proteome palmitoylation profiling with a bioorthogonal alkyne-palmitate reporter demonstrated specific inhibition of Hhat in cells. RUSKI-201 is the first selective Hhat chemical probe in cells and should be used in future studies of Hhat catalytic function.
AU - Rodgers,U
AU - Lanyon-Hogg,T
AU - Masumoto,N
AU - Ritzefeld,M
AU - Burke,R
AU - Blagg,J
AU - Magee,A
AU - Tate,E
DO - 10.1021/acschembio.6b00896
EP - 3262
PY - 2016///
SN - 1554-8937
SP - 3256
TI - Characterization of hedgehog acyltransferase inhibitors identifies a small molecule probe for hedgehog signaling by cancer cells
T2 - ACS Chemical Biology
UR - http://dx.doi.org/10.1021/acschembio.6b00896
UR - http://hdl.handle.net/10044/1/41906
VL - 11
ER -
