Evidence map›Paper›PMID 34992247›Full record

ArticleNature biotechnology2022

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

Christopher W Davies, Angela J Oh, Rana Mroue, Micah Steffek, John M Bruning, Yang Xiao, Siyu Feng, Sangeeta Jayakar, Emily Chan, Vidhyalakshmi Arumugam and 17 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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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

27 authors.

Christopher W Davies *Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA.
Angela J Oh *Department of Structural Biology, Genentech, Inc., South San Francisco, CA, USA.
Rana Mroue *Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.
Micah Steffek *Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
John M BruningDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
Yang XiaoDepartment of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.
Siyu FengDepartment of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.
Sangeeta JayakarDepartment of Pathology, Genentech, Inc., South San Francisco, CA, USA.
Emily ChanDepartment of Translational Oncology, Genentech, Inc., South San Francisco, CA, USA.
Vidhyalakshmi ArumugamDepartment of Translational Oncology, Genentech, Inc., South San Francisco, CA, USA.
Sean Carlo UribeDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
Jake DrummondDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
Alexandra FrommletDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
Cheng LuDepartment of Protein Chemistry, Genentech, Inc., South San Francisco, CA, USA.
Yvonne FrankeDepartment of BioMolecular Resources, Genentech, Inc., South San Francisco, CA, USA.
Mark MerchantDepartment of Translational Oncology, Genentech, Inc., South San Francisco, CA, USA.
Hartmut KoeppenDepartment of Pathology, Genentech, Inc., South San Francisco, CA, USA.
John G QuinnDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA.
Sushant MalhotraDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.
Steve DoDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.
Lewis GazzardDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.
Hans E PurkeyDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8570-364X
Joachim RudolphDepartment of Discovery Chemistry, Genentech, Inc., South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0806-6106
Melinda M MulvihillDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, CA, USA. mulvihill.melinda@gene.com.
James T KoerberDepartment of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA. koerber.james@gene.com.ORCID http://orcid.org/0000-0001-7756-972X
Weiru WangDepartment of Structural Biology, Genentech, Inc., South San Francisco, CA, USA. wang.weiru@gene.com.
Marie EvangelistaDepartment of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA. evangelista.marie@gene.com.ORCID http://orcid.org/0000-0003-4623-1595

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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

Indexed as

AntibodiesNeoplasmsProto-Oncogene Proteins p21(ras)HumansLigandsMutationAntibodiesKRAS protein, humanLigandsProto-Oncogene Proteins p21(ras)

Identifiers

PMID34992247

What OpenQuestion holds

Textmetadata
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.