Inhibition and degradation of NRAS with a pan-NRAS monobody.
Michael Whaby, Gayatri Ketavarapu, Akiko Koide, Megan Mazzei, Mubashir Mintoo, Eliezra Glasser, Unnatiben Patel, Cecile Nasarre, Matthew J Sale, Frank McCormick and 2 more
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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.
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
12 authors.
Michael WhabyDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Gayatri KetavarapuPerlmutter Cancer Center, New York University Langone Health, New York, NY, USA.
Akiko KoidePerlmutter Cancer Center, New York University Langone Health, New York, NY, USA.ORCID 0000-0003-1796-7077
Megan MazzeiDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Mubashir MintooDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Eliezra GlasserPerlmutter Cancer Center, New York University Langone Health, New York, NY, USA.ORCID 0000-0002-1371-4980
Unnatiben PatelPerlmutter Cancer Center, New York University Langone Health, New York, NY, USA.
Cecile NasarreDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Matthew J SaleHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Frank McCormickHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6619-7120
Shohei KoidePerlmutter Cancer Center, New York University Langone Health, New York, NY, USA. shohei.koide@nyulangone.org.ORCID 0000-0001-5473-4358
John P O'BryanDepartment of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA. obryanjo@musc.edu.ORCID 0000-0001-5386-1080
Funding
Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI John J Lemasters · 2009 to 2026
$42.7M
The role of SMAD1 and SATB2 in colon patterningP20GM130457 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Jennifer Susan Stancill · 2020 to 2026
$18.7M
Probing RAS-mediated Signaling with Monobody InhibitorsR01CA212608 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SHOHEI KOIDE, John P O'Bryan · 2017 to 2026
$5.8M
Cellular, Biochemical and Molecular Sciences Training Program: Developing the skills and expertise needed for a changing biomedical landscapeT32GM132055 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Amy D Bradshaw, John P O'Bryan · 2019 to 2026
$3.9M
Molecular mechanisms of SHP2 signaling dissected with designer binding proteinsR01CA194864 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KOIDE, SHOHEI · 2016 to 2020
$1.8M
Novel Functions for Ras Family GTPasesI01BX002095 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI O'BRYAN, JOHN P · 2014 to 2024
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BLRD VA I01 BX002095NCI NIH HHS P30 CA016087NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA194864NCI NIH HHS R01 CA212608NIGMS NIH HHS P20 GM130457NIGMS NIH HHS T32 GM132055U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA016087U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA138313U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA194864U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA212608U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM130457U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM132055U.S. Department of Veterans Affairs (Department of Veterans Affairs) BX002095
6 · The paper itself
Abstract
The RAS family GTPases are the most frequently mutated oncogene family in human cancers. Activating mutations in either of the three RAS isoforms (HRAS, KRAS, or NRAS) are found in nearly 20% of all human tumors with NRAS mutated in ~25% of melanomas. Despite remarkable advancements in therapies targeted against mutant KRAS, NRAS-specific pharmacologics are lacking. Thus, development of inhibitors of NRAS would address a critical unmet need to treating primary tumors harboring NRAS mutations as well as BRAF-mutant melanomas, which frequently develop resistance to clinically approved BRAF inhibitors through NRAS mutation. Building upon our previous studies with the monobody NS1 that recognizes HRAS and KRAS but not NRAS, here we report the development of a monobody that specifically binds to both GDP and GTP-bound states of NRAS and inhibits NRAS-mediated signaling in a mutation-agnostic manner. Further, this monobody can be formatted into a genetically encoded NRAS-specific degrader. Our study highlights the feasibility of developing NRAS selective inhibitors for therapeutic efforts.
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.
Inhibition and degradation of NRAS with a pan-NRAS monobody. · full record | OpenQuestion