ArticleACS chemical biology2016
Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Impact of Hedgehog modulators on signaling pathways in primary murine and human hepatocytes in vitro: insights into liver metabolism.Archives of toxicology · 2025Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer.International journal of molecular sciences · 2024Review
- Design, Synthesis, and Evaluation of Inhibitors of Hedgehog Acyltransferase.Journal of medicinal chemistry · 2024Article
- Cellular and molecular mechanisms of Hedgehog signalling.Nature reviews. Molecular cell biology · 2023Review
- Mechanism of action for small-molecule inhibitors of triacylglycerol synthesis.Nature communications · 2023Article
- A rising tide lifts all MBOATs: recent progress in structural and functional understanding of membrane boundFrontiers in physiology · 2023Review
- Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.Frontiers in oncology · 2022Review
- Structure, mechanism, and inhibition of Hedgehog acyltransferase.Molecular cell · 2021Article
- Review
- A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications.Chemical reviews · 2021Review
- Photochemical Probe Identification of a Small-Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT).Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- Photochemical Probe Identification of a Small-Molecule Inhibitor Binding Site in Hedgehog Acyltransferase (HHAT)*.Angewandte Chemie (International ed. in English) · 2021Article
- Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review).International journal of molecular medicine · 2021Review
- NKX6-1 mediates cancer stem-like properties and regulates sonic hedgehog signaling in leiomyosarcoma.Journal of biomedical science · 2021Article
- Palmitoylation of Hedgehog proteins by Hedgehog acyltransferase: roles in signalling and disease.Open biology · 2021Review
- Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling.Trends in biochemical sciences · 2020Review
- Targeted and proteome-wide analysis of metabolite-protein interactions.Current opinion in chemical biology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.