Evidence map›Paper›PMID 42365001›Full record

ArticleNature communications2026

Covalent pan-TEAD inhibitors block YAP activity and demonstrate brain penetrance in a Hippo-dependent cancer model.

Thijs J Hagenbeek, Jason Zbieg, Russell Smith, Sayantanee Paul, Luca Gerosa, Consuelo Torrini, Alissa D Guarnaccia, Christy Ong, Jennifer A Lacap, Miaoran Ning and 44 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

54 authors.

Thijs J Hagenbeek *Department of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Jason Zbieg *Department of Discovery Chemistry, Genentech, South San Francisco, CA, USA.
Russell Smith *Department of Discovery Chemistry, Genentech, South San Francisco, CA, USA.
Sayantanee Paul *Department of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Luca Gerosa *Department of gRED Computational Sciences, Genentech, South San Francisco, CA, USA.
Consuelo TorriniDepartment of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2743-0839
Alissa D GuarnacciaDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4195-2158
Christy OngDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Jennifer A LacapDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Miaoran NingDepartment of Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, CA, USA.
Nicole M SodirDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Marc HafnerDepartment of gRED Computational Sciences, Genentech, South San Francisco, CA, USA.
Julien TremblayDepartment of gRED Computational Sciences, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6085-3481
James HawleyDepartment of gRED Computational Sciences, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4744-5552
Bryan ChanDepartment of Discovery Chemistry, Genentech, South San Francisco, CA, USA.
Vishal A VermaDepartment of Discovery Chemistry, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7600-4372
Ramsay E BeveridgeParaza Pharma Inc, Montreal, QC, Canada.
Peter L HsuDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9381-6564
Gözde UlasDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Lisha WangDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Jim NonomiyaDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Shu ChenDepartment of Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, CA, USA.
Victoria PhamDepartment of Proteomic and Genomic Technologies, Genentech, South San Francisco, CA, USA.
Joshua WebsterDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0014-1685
Jessica PrestonDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Jeff HungDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Jeff EasthamDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Debra DunlapDepartment of Research Pathology, Genentech, South San Francisco, CA, USA.
Wendy LeeDepartment of Discovery Chemistry, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9959-8529
Paul BerozaDepartment of Discovery Chemistry, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9407-1648
Naema NayyarDepartment of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Scott MartinDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Eva LinDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Julie WengDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Scott A FosterDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Frances ShanahanDepartment of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Rina FongDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.
Gladys BoenigDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8314-1188
Paola Di LelloDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9683-926X
Marta H KubalaDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.
Thomas HunsakerDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Mirunalini RavichandranDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Pablo Saenz-Lopez LarrochaDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Jeffrey LauDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Le AnDepartment of Small Molecule Pharmaceutical Sciences, Genentech, South San Francisco, CA, USA.
Elizabeth LevyDepartment of Small Molecule Pharmaceutical Sciences, Genentech, South San Francisco, CA, USA.
Maria N LorenzoDepartment of Protein Chemistry, Genentech, South San Francisco, CA, USA.
Jennie R LillDepartment of Proteomic and Genomic Technologies, Genentech, South San Francisco, CA, USA.
Zora D ModrusanDepartment of Proteomic and Genomic Technologies, Genentech, South San Francisco, CA, USA.
Yi-Chen ChenDepartment of Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, CA, USA.
Xiaosai YaoDepartment of gRED Computational Sciences, Genentech, South San Francisco, CA, USA.
Priscilla K BrastianosDepartment of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4470-8425
Danilo Maddalo *Department of Translational Oncology, Genentech, South San Francisco, CA, USA. maddalo.danilo@gene.com.ORCID http://orcid.org/0000-0002-3228-1703
Anwesha Dey *Department of Discovery Oncology, Genentech, South San Francisco, CA, USA. dey.anwesha@gene.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TEAD transcription factors enable the oncogenic activity of deregulated Hippo signaling and are a promising therapeutic target in oncology. Targeting the TEAD lipid pocket is an established path to inhibit the oncogenic activities of cofactors YAP and TAZ. Here we present two pan-TEAD inhibitors, GNE-8025 and its in vivo brain-penetrant derivative GNE-2181, that covalently bind the lipid pocket at a conserved cysteine. Both small molecules show growth inhibition of YAP-driven tumor cells in vitro and in vivo. Moreover, we show that GNE-8025 increases the activity of a broad range of MAPK pathway inhibitors in vitro as well as the KRAS

Indexed as

Adaptor Proteins, Signal TransducingAntineoplastic AgentsBrainBrain NeoplasmsDNA-Binding ProteinsProtein Serine-Threonine KinasesTranscription FactorsAnimalsCell Line, TumorCell ProliferationFemaleHippo Signaling PathwayHumansMiceSignal TransductionTEA Domain Transcription FactorsAdaptor Proteins, Signal TransducingAntineoplastic AgentsDNA-Binding ProteinsProtein Serine-Threonine KinasesTEA Domain Transcription FactorsTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins

Identifiers

PMID42365001
PMCPMC13454592

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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.