PXD031185

PXD031185 is an original dataset announced via ProteomeXchange.

Title	Addressing Enzymatic-Independent Tumor-Promoting Function of NAMPT via two PROTAC-Mediated Degradation
Description	The rate-limiting enzyme of salvage pathway for NAD+ synthesis, NAMPT, is aberrantly overexpressed in a variety of tumor cells and is a poor prognosis factor for patient survival. NAMPT plays a major role in tumor cell proliferation, acting concurrently as an NAD+ synthase and unexpectedly, an extracellular ligand for several tumor-promoting signaling pathways. While previous efforts to modulate NAMPT activity were limited to enzymatic inhibitors with low success in clinical studies, protein degradation offers a possibility to simultaneously disrupt NAMPT’s enzyme activity and ligand capabilities. Here, we report the development of two highly selective NAMPT-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent NAMPT degradation in a cereblon-dependent manner in multiple tumor cell lines. Notably, both PROTAC degraders outperform a clinical candidate, FK866, in killing effect on hematological tumor cells. These results emphasize the importance and feasibility of applying PROTACs a
HostingRepository	iProX
AnnounceDate	2022-01-24
AnnouncementXML	Submission_2023-12-24_20:27:25.198.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaotong Zhu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-24 01:13:04	ID requested
⏵ 1	2023-12-24 20:27:25	announced

Zhu X, Liu H, Chen L, Wu C, Liu X, Cang Y, Jiang B, Yang X, Fan G, Addressing the Enzyme-independent tumor-promoting function of NAMPT via PROTAC-mediated degradation. Cell Chem Biol, 29(11):1616-1629.e12(2022) [pubmed]

submitter keyword: PROTAC, iNAMPT, eNAMPT, enzymatic-independent, NAD+

Gaofeng Fan
contact affiliation	Shanghaitech Univercity
contact email	fangf@shanghaitech.edu.cn
lab head
Xiaotong Zhu
contact affiliation	Shanghaitech Univercity
contact email	834988204@qq.com
dataset submitter

iProX dataset URI