Synonyms: DT-2216
Compound class:
Synthetic organic
Comment: DT2216 is a clinical stage PROTAC type protein degarder. It targets the BCL-XL protein (an anti-apoptotic protein that is overexpressed by some cancers) for degradation via the Von Hippel-Lindau (VHL) E3 ligase, and was developed for potential antitumour activity [2,4]. In vivo (in mice), The target protein binding moiety is based on the BCL-XL protein antagonist navitoclax (ABT-263) [2]. Since VHL is poorly expressed in platelets, DT2216 is significantly less toxic to platelets than parental navitoclax.
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References |
1. He Y, Koch R, Budamagunta V, Zhang P, Zhang X, Khan S, Thummuri D, Ortiz YT, Zhang X, Lv D et al.. (2020)
DT2216-a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas. J Hematol Oncol, 13 (1): 95. [PMID:32677976] |
2. Khan S, Zhang X, Lv D, Zhang Q, He Y, Zhang P, Liu X, Thummuri D, Yuan Y, Wiegand JS et al.. (2019)
A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat Med, 25 (12): 1938-1947. [PMID:31792461] |
3. Zhang X, Thummuri D, Liu X, Hu W, Zhang P, Khan S, Yuan Y, Zhou D, Zheng G. (2020)
Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity. Eur J Med Chem, 192: 112186. [PMID:32145645] |
4. (2020)
The PROTAC DT2216 Targets Cancer by Promoting BCL-XL Degradation. Cancer Discov, 10 (2): 174. [PMID:34365411] |