Evidence map›Paper›PMID 32619469›Full record

ArticleMolecular cell2020

Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent.

Marco Jost, Yuwen Chen, Luke A Gilbert, Max A Horlbeck, Lenno Krenning, Grégory Menchon, Ankit Rai, Min Y Cho, Jacob J Stern, Andrea E Prota and 5 more

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

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.4field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 58 citations in OpenAlex.

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  17. Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent.International journal of molecular sciences · 2023
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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

15 authors at 5 institutions in 3 countries.

Marco JostDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Yuwen ChenDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Luke A GilbertDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA.
Max A HorlbeckDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Lenno KrenningHubrecht Institute - KNAW and University Medical Center Utrecht, 3584CT Utrecht, the Netherlands.
Grégory MenchonLaboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland.
Ankit RaiCell Biology, Department of Biology, Faculty of Science, Utrecht University, 3548CH Utrecht, the Netherlands.
Min Y ChoDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Jacob J SternDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Andrea E ProtaLaboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland.
Martin KampmannDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Neurodegenerative Diseases and Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Chan-Zuckerberg Biohub, San Francisco, CA 94158, USA.
Anna AkhmanovaCell Biology, Department of Biology, Faculty of Science, Utrecht University, 3548CH Utrecht, the Netherlands.
Michel O SteinmetzLaboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland; Biozentrum, University of Basel, 4056 Basel, Switzerland.
Marvin E TanenbaumHubrecht Institute - KNAW and University Medical Center Utrecht, 3584CT Utrecht, the Netherlands. Electronic address: m.tanenbaum@hubrecht.eu.
Jonathan S WeissmanDepartment of Cellular & Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: jonathan.weissman@ucsf.edu.
Howard Hughes Medical Institute · USPaul Scherrer Institute · CHUniversity Medical Center Utrecht · NLUtrecht University · NLUniversity of Basel · CH

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
PROJECT 3P50GM102706 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2012 to 2016
$9.5M
Bay Area Cancer Target Discovery and Development NetworkU01CA168370 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCCORMICK, FRANK PATRICK, MCMANUS, MICHAEL T · 2012 to 2016
$3.9M
Harnessing CRISPR for Targeted and Inducible Epigenomic ReprogrammingR01DA036858 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A, QI, LEI STANLEY · 2013 to 2017
$2.9M
Systematic Genome-Wide Characterization of Iron HomeostasisF32GM116331 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOST, MARCO · 2015 to 2017
$162k
A functional genomics approach to determine the mechanism of cellular response to new anti-cancer drugsK99CA204602 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2016 to 2016
$139k
Stress response networks in cancer: systematic mapping and therapeutic potentialK99CA181494 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN · 2014 to 2014
$139k
NCI NIH HHS K99 CA181494NCI NIH HHS K99 CA204602NCI NIH HHS U01 CA168370NIDA NIH HHS R01 DA036858NIGMS NIH HHS F32 GM116331NIGMS NIH HHS P50 GM102706NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

We recently used CRISPRi/a-based chemical-genetic screens and cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. Reddy and co-workers (Baker et al., 2020, this issue of Molecular Cell) suggest that a contaminating degradation product in commercial formulations of rigosertib is responsible for the microtubule-destabilizing activity. Here, we demonstrate that cells treated with pharmaceutical-grade rigosertib (>99.9% purity) or commercially obtained rigosertib have qualitatively indistinguishable phenotypes across multiple assays. The two formulations have indistinguishable chemical-genetic interactions with genes that modulate microtubule stability, both destabilize microtubules in cells and in vitro, and expression of a rationally designed tubulin mutant with a mutation in the rigosertib binding site (L240F TUBB) allows cells to proliferate in the presence of either formulation. Importantly, the specificity of the L240F TUBB mutant for microtubule-destabilizing agents has been confirmed independently. Thus, rigosertib kills cancer cells by destabilizing microtubules, in agreement with our original findings.

Indexed as

Cell ProliferationAntineoplastic AgentsCells, CulturedCrystallography, X-RayDrug ContaminationGlycineHumansMicrotubulesMutationNeoplasmsPharmaceutical PreparationsProtein ConformationSulfonesTubulinAntineoplastic AgentsGlycineON 01910Pharmaceutical PreparationsSulfonesTubulinchemical geneticsCRISPRaCRISPRidrug mechanism of actiondrug target identificationmicrotubulesrigosertib

Identifiers

PMID32619469
PMCPMC7332992
OpenAlexW3038900729

What OpenQuestion holds

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Registered trials

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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.