Evidence map›Paper›PMID 32568509›Full record

ArticleACS chemical biology2020

Inhibition of NRAS Signaling in Melanoma through Direct Depalmitoylation Using Amphiphilic Nucleophiles.

Hetika D Vora, Mai Johnson, Roberto J Brea, Andrew K Rudd, Neal K Devaraj

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.Expert review of precision medicine and drug development · 2021
    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

5 authors at 1 institution in 1 country.

Hetika D VoraDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 3328, La Jolla, California 92093, United States.ORCID 0000-0002-0647-7446
Mai JohnsonDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 3328, La Jolla, California 92093, United States.
Roberto J BreaDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 3328, La Jolla, California 92093, United States.ORCID 0000-0002-0321-0156
Andrew K RuddDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 3328, La Jolla, California 92093, United States.
Neal K DevarajDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 3328, La Jolla, California 92093, United States.ORCID 0000-0002-8033-9973
University of California San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Amplifying PET Imaging Signals for In Vivo Detection of Pancreatic Beta-cellsDP2DK111801 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVARAJ, NEAL KRISHNA · 2016 to 2018
$2.0M
NCI NIH HHS P30 CA023100NCI NIH HHS T32 CA009523NIDDK NIH HHS DP2 DK111801NIGMS NIH HHS T32 GM008326
6 · The paper itself

Abstract

Activating mutations in the small GTPase NRAS are responsible for driving tumor growth in several cancers. Unfortunately, the development of NRAS inhibitors has proven difficult due to the lack of hydrophobic binding pockets on the protein's surface. To overcome this limitation, we chose to target the post-translational S-palmitoyl modification of NRAS, which is required for its signaling activity. Utilizing an amphiphile-mediated depalmitoylation (AMD) strategy, we demonstrate the ability to directly cleave S-palmitoyl groups from NRAS and inhibit its function. C8 alkyl cysteine causes a dose-dependent decrease in NRAS palmitoylation and inhibits downstream signaling in melanoma cells with an activating mutation in NRAS. This compound reduces cell growth in NRAS-driven versus non-NRAS-driven melanoma lines and inhibits tumor progression in an NRAS-mutated melanoma xenograft mouse model. Our work demonstrates that AMD can effectively suppress NRAS activity and could represent a promising new avenue for discovering lead compounds for treatment of NRAS-driven cancers.

Indexed as

LipoylationSignal TransductionApoptosisCell Line, TumorCell ProliferationGTP PhosphohydrolasesHeLa CellsHumansMelanomaMembrane ProteinsProtein Kinase InhibitorsSkin NeoplasmsGTP PhosphohydrolasesMembrane ProteinsNRAS protein, humanProtein Kinase Inhibitors

Identifiers

PMID32568509
PMCPMC7556697
OpenAlexW3036950133

What OpenQuestion holds

Textmetadata
LicenceTDM
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.