PXD039828

PXD039828 is an original dataset announced via ProteomeXchange.

Title	Development and characterization of selective FAK inhibitors and PROTACs with in vivo activity
Description	Focal adhesion kinase (FAK) is an attractive drug target due to its overexpression in cancer. FAK functions as a non-receptor tyrosine kinase and scaffolding protein, coordinating several downstream signaling effectors and cellular processes. While drug discovery efforts have largely focused on targeting FAK kinase activity, FAK inhibitors have failed to show efficacy as single agents in clinical trials. Here, using structure-guided design, we report the development of a selective FAK inhibitor (BSJ-04-175) and degrader (BSJ-04-146) to evaluate the consequences and advantages of abolishing all FAK activity in cancer models. BSJ-04-146 achieves rapid and potent FAK degradation with high proteome-wide specificity in cancer cells and induces remarkably durable degradation in tumor-bearing mice. Compared to kinase inhibition, targeted degradation of FAK exhibits pronounced improved activity on downstream signaling and cancer cell viability and migration. Together, BSJ-04-175 and BSJ-04-146 are valuable chemical tools to dissect the specific consequences of targeting FAK through small molecule inhibition or degradation.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:25:58.532.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Behnam Nabet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-03 06:02:19	ID requested
⏵ 1	2025-05-06 09:25:59	announced

Koide E, Mohardt ML, Doctor ZM, Yang A, Hao M, Donovan KA, Kuismi CC, Nelson AJ, Abell K, Aguiar M, Che J, Stokes MP, Zhang T, Aguirre AJ, Fischer ES, Gray NS, Jiang B, Nabet B, Development and Characterization of Selective FAK Inhibitors and PROTACs with In Vivo Activity. Chembiochem, 24(19):e202300141(2023) [pubmed]

10.1002/cbic.202300141;

submitter keyword: FAK, inhibitor, PROTAC, degrader

Behnam Nabet
contact affiliation	Fred Hutch Cancer Center, Human Biology Division
contact email	bnabet@fredhutch.org
lab head
Behnam Nabet
contact affiliation	Fred Hutchinson Cancer Center
contact email	bnabet@fredhutch.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD039828

PRIDE project URI

• PRIDE
  1. PXD039828
     1. Label: PRIDE project
     2. Name: Development and characterization of selective FAK inhibitors and PROTACs with in vivo activity