PXD028453-2
PXD028453 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: PROTAC, iNAMPT, eNAMPT, enzymatic-independent, NAD+ |
Contact List
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 |
Full Dataset Link List
iProX dataset URI |