Evidence map›Paper›PMID 34666187›Full record

ArticleBioorganic & medicinal chemistry letters2021

Chemical proteomic analysis of palmostatin beta-lactone analogs that affect N-Ras palmitoylation.

Radu M Suciu, Irungu K Luvaga, Akram Hazeen, Chulangani Weerasooriya, Stewart K Richardson, Ari J Firestone, Kevin Shannon, Amy R Howell, Benjamin F Cravatt

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Radu M SuciuDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Irungu K LuvagaDepartment of Chemistry, University of Connecticut, Storrs, CT, USA.
Akram HazeenDepartment of Chemistry, University of Connecticut, Storrs, CT, USA.
Chulangani WeerasooriyaDepartment of Chemistry, University of Connecticut, Storrs, CT, USA.
Stewart K RichardsonDepartment of Chemistry, University of Connecticut, Storrs, CT, USA.
Ari J FirestoneDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Kevin ShannonDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Amy R HowellDepartment of Chemistry, University of Connecticut, Storrs, CT, USA. Electronic address: amy.howell@uconn.edu.
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: cravatt@scripps.edu.
University of Connecticut · USScripps Research Institute · USUniversity of California, San Francisco · US

Funding

Chemical Proteomic Platforms for Radically Expanding Cancer DruggabilityR35CA231991 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BENJAMIN F CRAVATT · 2018 to 2026
$9.5M
Selectively Targeting Oncogenic NRAS in CancerR01CA193994 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KEVIN M. SHANNON · 2015 to 2026
$5.8M
The role of mTORC2 in reprogramming cancer cell metabolismR01NS073831 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MISCHEL, PAUL S · 2011 to 2020
$3.4M
Translational Investigation of KRas & NF1 in Myeloid LeukemiaR37CA072614 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHANNON, KEVIN M. · 2007 to 2016
$3.4M
Integrated ligand and target discovery by chemical proteomics for glioblastoma treatment.R01CA238249 · NCI · STANFORD UNIVERSITY · PI CRAVATT, BENJAMIN F, MISCHEL, PAUL S · 2021 to 2025
$3.3M
Translational Investigation of NF1 in Myeloid LuekemiaR01CA072614 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHANNON, KEVIN M. · 1997 to 2006
$2.0M
NCI NIH HHS R01 CA072614NCI NIH HHS R01 CA193994NCI NIH HHS R01 CA238249NCI NIH HHS R35 CA231991NCI NIH HHS R37 CA072614NINDS NIH HHS R01 NS073831
6 · The paper itself

Abstract

S-Palmitoylation is a reversible post-translational lipid modification that regulates protein trafficking and signaling. The enzymatic depalmitoylation of proteins is inhibited by the beta-lactones Palmostatin M and B, which have been found to target several serine hydrolases. In efforts to better understand the mechanism of action of Palmostatin M, we describe herein the synthesis, chemical proteomic analysis, and functional characterization of analogs of this compound. We identify Palmostatin M analogs that maintain inhibitory activity in N-Ras depalmitoylation assays while displaying complementary reactivity across the serine hydrolase class as measured by activity-based protein profiling. Active Palmostatin M analogs inhibit the recently characterized ABHD17 subfamily of depalmitoylating enzymes, while sparing other candidate depalmitoylases such as LYPLA1 and LYPLA2. These findings improve our understanding of the structure-activity relationship of Palmostatin M and refine the set of serine hydrolase targets relevant to the compound's effects on N-Ras palmitoylation dynamics.

Indexed as

ProteomicsHumansLactonesMolecular StructurePropiolactoneras ProteinsSulfonesLactonespalmostatin MPropiolactoneras ProteinsSulfonesActivity-based protein profilingPalmitoylation

Identifiers

PMID34666187
PMCPMC8896339
OpenAlexW3205006332

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.