PXD028453

PXD028453 is an original dataset announced via ProteomeXchange.

Title	Addressing Enzymatic-Independent Tumor-Promoting Function of NAMPT via 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 a NAD+ synthase and unexpectedly, an extracellular ligand for several tumor-promoting signaling pathway. 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 as a better strategy for targeting proteins like NAMPT with dual tumor-promoting functions, which are not easily achieved by conventional enzymatic inhibitors.
HostingRepository	iProX
AnnounceDate	2021-09-13
AnnouncementXML	Submission_2023-12-21_20:36:18.290.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	2021-09-13 19:01:00	ID requested
1	2021-10-03 01:31:29	announced
⏵ 2	2023-12-21 20:36:19	announced	2023-12-22: Update publication information.

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 University
contact email	fangf@shanghaitech.edu.cn
lab head
Xiaotong Zhu
contact affiliation	ShanghaiTech University
contact email	zhuxt@shanghaitech.edu.cn
dataset submitter

iProX dataset URI