Conformation-locking antibodies for the discovery and characterization of KRAS inhibitors.

Antibodies / chemistry Humans Ligands Mutation Neoplasms Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors

Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
05 2022
Historique:
received: 07 01 2021
accepted: 07 10 2021
pubmed: 8 1 2022
medline: 20 5 2022
entrez: 7 1 2022
Statut: ppublish

Résumé

Small molecules that stabilize inactive protein conformations are an underutilized strategy for drugging dynamic or otherwise intractable proteins. To facilitate the discovery and characterization of such inhibitors, we created a screening platform to identify conformation-locking antibodies for molecular probes (CLAMPs) that distinguish and induce rare protein conformational states. Applying the approach to KRAS, we discovered CLAMPs that recognize the open conformation of KRAS

Identifiants

DOI: 10.1038/s41587-021-01126-9 PMID: 34992247
pubmed: 34992247
doi: 10.1038/s41587-021-01126-9
pii: 10.1038/s41587-021-01126-9
doi:

Substances chimiques

Antibodies 0
KRAS protein, human 0
Ligands 0
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

769-778

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Christopher W Davies (CW)

Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA.

Angela J Oh (AJ)

Department of Structural Biology, Genentech, Inc., South San Francisco, CA, USA.

Rana Mroue (R)

Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.

Micah Steffek (M)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.

John M Bruning (JM)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.

Yang Xiao (Y)

Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.

Siyu Feng (S)

Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.

Sangeeta Jayakar (S)

Department of Pathology, Genentech, Inc., South San Francisco, CA, USA.

Emily Chan (E)

Department of Translational Oncology, Genentech, Inc., South San Francisco, CA, USA.

Vidhyalakshmi Arumugam (V)

Department of Translational Oncology, Genentech, Inc., South San Francisco, CA, USA.

Sean Carlo Uribe (SC)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.

Jake Drummond (J)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.

Alexandra Frommlet (A)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.

Cheng Lu (C)

Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA, USA.

Yvonne Franke (Y)

Department of BioMolecular Resources, Genentech, Inc., South San Francisco, CA, USA.

Mark Merchant (M)

Department of Translational Oncology, Genentech, Inc., South San Francisco, CA, USA.

Hartmut Koeppen (H)

Department of Pathology, Genentech, Inc., South San Francisco, CA, USA.

John G Quinn (JG)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.

Sushant Malhotra (S)

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.

Steve Do (S)

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.

Lewis Gazzard (L)

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.

Hans E Purkey (HE)

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.
ORCID: 0000-0002-8570-364X

Joachim Rudolph (J)

Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.
ORCID: 0000-0002-0806-6106

Melinda M Mulvihill (MM)

Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA. mulvihill.melinda@gene.com.

James T Koerber (JT)

Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA. koerber.james@gene.com.
ORCID: 0000-0001-7756-972X

Weiru Wang (W)

Department of Structural Biology, Genentech, Inc., South San Francisco, CA, USA. wang.weiru@gene.com.

Marie Evangelista (M)

Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA. evangelista.marie@gene.com.
ORCID: 0000-0003-4623-1595

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Conformation-locking antibodies for the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Conformation-locking antibodies for the...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Conformation-locking antibodies for the...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Conformation-locking antibodies for the...
questionsmedicales.fr › Tumeurs › Conformation-locking antibodies for the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes p21(ras) › Conformation-locking antibodies for the...