PXD062889

PXD062889 is an original dataset announced via ProteomeXchange.

Title	Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation
Description	PKMYT1 has recently emerged as a compelling therapeutic target for precision cancer therapy due to its synthetic lethality with oncogenic alterations such as CCNE1 amplification and mutations in FBXW7 and PPP2R1A. Current small molecule PKMYT1 inhibitors face limitations, such as insufficient molecular diversity and poor selectivity. We used our generative AI platform to develop a bifunctional PKMYT1 degrader by linking an entirely novel PKMYT1 inhibitor to an optimized cereblon (CRBN) binder. The lead PROTAC D16-M1P2 demonstrated dual mechanisms of PKMYT1 degradation and antagonism, with strong antiproliferative potency facilitated by high selectivity. It also exhibited favorable oral bioavailability, stronger pharmacodynamic effects relative to the PKMYT1 inhibitor alone, and robust antitumor response as a monotherapy in xenograft models. This first-in-class PROTAC serves as a precise chemical probe to explore PKMYT1 biology and a promising lead for further cancer therapy exploration.
HostingRepository	PRIDE
AnnounceDate	2025-09-28
AnnouncementXML	Submission_2025-09-27_20:12:18.610.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaomin Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-13 13:02:22	ID requested
⏵ 1	2025-09-27 20:12:19	announced

Dataset with its publication pending

submitter keyword: PROTAC,PKMYT1, synthetic lethality, AI-generation

Xin Cai
contact affiliation	Insilico Meidicine Shanghai Ltd.
contact email	xin.cai@insilico.ai
lab head
Xiaomin Wang
contact affiliation	Insilico Medicine Shanghai Ltd
contact email	xiaomin.wang@insilico.ai
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/2025/09/PXD062889

PRIDE project URI

• PRIDE
  1. PXD062889
     1. Label: PRIDE project
     2. Name: Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation