PXD040941-1

PXD040941 is an original dataset announced via ProteomeXchange.

Title	Discovery of a Highly Potent and Selective HDAC3 and HDAC8 PROTAC Dual Degrader
Description	HDAC3 and HDAC8 are members of class I deacetylases involved in several biological mechanisms and represent a highly sought-after therapeutic target for drug development. It is historically challenging to develop selective deacetylase inhibitors due to their conserved catalytic domains. HDAC3 also has deacetylase-independent activity, which cannot be blocked by conventional enzymatic inhibitors. Recent advances in proteolysis-targeting chimeras (PROTACs) provides an opportunity to eliminate the whole protein selectively, abolishing both enzymatic and scaffolding functions. Here, we report a novel HDAC3/8 dual degrader YX968 that induces highly potent, rapid and selective degradation of both HDAC3 and HDAC8 without trigging pan-HDAC inhibitory effects. Unbiased quantitative proteomics experiments further confirmed its high selectivity. This dual-specific degrader specifically ablates cellular pathways attributed to HDAC3 and HDAC8 and exhibits high potency in killing cancer cells. YX968 represents a new probe for dissecting the complex biological functions of HDAC3 and HDAC8.
HostingRepository	PRIDE
AnnounceDate	2023-07-18
AnnouncementXML	Submission_2023-07-18_08:05:24.022.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	EricFischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-17 07:35:54	ID requested
⏵ 1	2023-07-18 08:05:24	announced
2	2024-10-22 05:54:12	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: epigenetics, HDAC3,PROTAC, histone deacetylase, HDAC8, degrader

EricFischer
contact affiliation	Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
EricFischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040941
     1. Label: PRIDE project
     2. Name: Discovery of a Highly Potent and Selective HDAC3 and HDAC8 PROTAC Dual Degrader