Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRAS


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
12 05 2022
Historique:
pubmed: 27 4 2022
medline: 18 5 2022
entrez: 26 4 2022
Statut: ppublish

Résumé

KRAS is an archetypal high-value intractable oncology drug target. The glycine to cysteine mutation at codon 12 represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach that led to the identification of

Identifiants

pubmed: 35471939
doi: 10.1021/acs.jmedchem.2c00369
doi:

Substances chimiques

Antineoplastic Agents 0
KRAS protein, human 0
Quinazolines 0
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

6940-6952

Auteurs

Jason G Kettle (JG)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Sharan K Bagal (SK)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Sue Bickerton (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Michael S Bodnarchuk (MS)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Scott Boyd (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Jason Breed (J)

Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Rodrigo J Carbajo (RJ)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Doyle J Cassar (DJ)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Atanu Chakraborty (A)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Sabina Cosulich (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Iain Cumming (I)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Michael Davies (M)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Nichola L Davies (NL)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Andrew Eatherton (A)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Laura Evans (L)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Lyman Feron (L)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Shaun Fillery (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Emma S Gleave (ES)

Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Frederick W Goldberg (FW)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Lyndsey Hanson (L)

Oncology R&D, AstraZeneca, Alderley Park SK10 4TG, U.K.

Stephanie Harlfinger (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Martin Howard (M)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Rachel Howells (R)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Anne Jackson (A)

Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Paul Kemmitt (P)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Gillian Lamont (G)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Scott Lamont (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Hilary J Lewis (HJ)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Libin Liu (L)

Pharmaron Beijing Co., Ltd., 6 Taihe Road BDA, Beijing 100176, P. R. China.

Michael J Niedbala (MJ)

Oncology R&D, AstraZeneca, Waltham, Massachusetts 02451, United States.

Christopher Phillips (C)

Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Radek Polanski (R)

Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Piotr Raubo (P)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Graeme Robb (G)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

David M Robinson (DM)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Sarah Ross (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Matthew G Sanders (MG)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Michael Tonge (M)

Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Rebecca Whiteley (R)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Stephen Wilkinson (S)

Oncology R&D, AstraZeneca, Cambridge CB4 0WG, U.K.

Junsheng Yang (J)

Pharmaron Beijing Co., Ltd., 6 Taihe Road BDA, Beijing 100176, P. R. China.

Wenman Zhang (W)

Pharmaron Beijing Co., Ltd., 6 Taihe Road BDA, Beijing 100176, P. R. China.

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Classifications MeSH