Evidence map›Paper›PMID 41766690›Full record

ArticleJournal of medicinal chemistry2026

Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C.

Nicholas F Endres, Steven Do, Rana Mroue, Jack A Terrett, Matt Saabye, Angela Oh, Thomas Hunsaker, Emily Chan, John C Tran, Lan K Nguyen and 42 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. 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

52 authors.

Nicholas F EndresGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0009-0005-1086-6048
Steven DoGenentech, Inc., South San Francisco, California 94080, United States.
Rana MroueGenentech, Inc., South San Francisco, California 94080, United States.
Jack A TerrettGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0001-8777-046X
Matt SaabyeConfluence Discovery Technologies, 4340 Duncan Ave., St. Louis, Missouri 63110, United States.
Angela OhGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0009-0004-0624-0619
Thomas HunsakerGenentech, Inc., South San Francisco, California 94080, United States.
Emily ChanGenentech, Inc., South San Francisco, California 94080, United States.
John C TranGenentech, Inc., South San Francisco, California 94080, United States.
Lan K NguyenGenentech, Inc., South San Francisco, California 94080, United States.
Qihui LianWuxi Apptec 288 Fu Te Zhong Lu, Wai Gaio Qiao Free Trade Zone, Shanghai 200131, China.
Taylur P MaGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0009-0005-7546-8366
Thomas GarnerGenentech, Inc., South San Francisco, California 94080, United States.
Luca GerosaGenentech, Inc., South San Francisco, California 94080, United States.
Maureen BeresiniGenentech, Inc., South San Francisco, California 94080, United States.
Aaron BoudreauGenentech, Inc., South San Francisco, California 94080, United States.
Sarah M BronnerGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0003-4370-6727
Patrick CyrGenentech, Inc., South San Francisco, California 94080, United States.
Noriko IshisokoGenentech, Inc., South San Francisco, California 94080, United States.
Yevgeniy IzrayelitGenentech, Inc., South San Francisco, California 94080, United States.
Fan JiangViva Biotech, No.735, Ziping Road, Pudong New Area, Shanghai 201318, China.
Terry KellarCrinetics Pharmaceuticals Inc, San Diego, California 92121-4718, United States.
Hank LaGenentech, Inc., South San Francisco, California 94080, United States.
Sharada LabadieGenentech, Inc., South San Francisco, California 94080, United States.
Matthew LardyGenentech, Inc., South San Francisco, California 94080, United States.
Liling LiuGenentech, Inc., South San Francisco, California 94080, United States.
Wendy LiuGenentech, Inc., South San Francisco, California 94080, United States.
Sarah MillerGenentech, Inc., South San Francisco, California 94080, United States.
Joachim RudolphGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0002-0806-6106
Emile PliseGenentech, Inc., South San Francisco, California 94080, United States.
Benjamin D SellersGenentech, Inc., South San Francisco, California 94080, United States.
Cheng ShaoPharmaron-Beijing Co. Ltd., 6 Taihe Road, BDA, Beijing 100176, China.
Weiru WangGenentech, Inc., South San Francisco, California 94080, United States.
Yanguang WangPharmaron-Beijing Co. Ltd., 6 Taihe Road, BDA, Beijing 100176, China.
Wentao WeiViva Biotech, No.735, Ziping Road, Pudong New Area, Shanghai 201318, China.
Susan WongGenentech, Inc., South San Francisco, California 94080, United States.
Christine YuGenentech, Inc., South San Francisco, California 94080, United States.
Kebing YuGenentech, Inc., South San Francisco, California 94080, United States.
Po-Wai YuenPharmaron-Beijing Co. Ltd., 6 Taihe Road, BDA, Beijing 100176, China.
Richard ZangGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0003-2875-6507
Chenghong ZhangGenentech, Inc., South San Francisco, California 94080, United States.
Yuhui ZhouWuxi Apptec 288 Fu Te Zhong Lu, Wai Gaio Qiao Free Trade Zone, Shanghai 200131, China.
Xiaoyu ZhuWuxi Apptec 288 Fu Te Zhong Lu, Wai Gaio Qiao Free Trade Zone, Shanghai 200131, China.
John G QuinnGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0002-4664-6232
Xin YeGenentech, Inc., South San Francisco, California 94080, United States.
James R KieferGenentech, Inc., South San Francisco, California 94080, United States.
Jialin MaoGenentech, Inc., South San Francisco, California 94080, United States.
Marie EvangelistaGenentech, Inc., South San Francisco, California 94080, United States.
Mark MerchantGenentech, Inc., South San Francisco, California 94080, United States.
Matthew L LandryGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0003-3202-2178
Sushant MalhotraGenentech, Inc., South San Francisco, California 94080, United States.
Hans E PurkeyGenentech, Inc., South San Francisco, California 94080, United States.ORCID 0000-0002-8570-364X

Funding

X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
NIGMS NIH HHS P41 GM103393
6 · The paper itself

Abstract

KRAS G12C is one of the most prevalent oncogenic mutations in nonsmall cell lung cancer. Herein we describe the discovery and optimization of divarasib (GDC-6036), an orally available, highly potent, and selective covalent KRAS G12C inhibitor. We demonstrate a significant noncovalent binding component of divarasib that contributes to its potency and rapid kinetics. Divarasib has greater potency and kinetics of alkylation compared with other KRAS G12C inhibitors

Indexed as

Antineoplastic AgentsDrug DiscoveryProto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorCell ProliferationHumansMiceStructure-Activity RelationshipAntineoplastic AgentsKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID41766690
PMCPMC12990036

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.