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link to J. Med. Chem. article: https://pubs.acs.org/doi/10.1021/acs.... channel email: [email protected] This video describes the discovery of DD205-291, a PROTAC-based degrader of HPK1 for the treatment of certain cancers. The content of this video was reported by scientists of Huadong Medicine in Hangzhou, China as a Drug Annotation article in the Journal of Medicinal Chemistry. The discovery project started with a previous Huadong compound, DD203, a HPK1 binder. Goals for the program included improving kinase selectivity and oral availability of the final PROTAC compound. The final compound, DD205-291, showed promising antitumor activity in rats when dosed in conjunction with an anti-PD1 antibody. At the time of publication, DD205-291 had filed an IND in China and the United States. This video was created for academic purposes. The creator of the video has no financial stake in the sponsor of the research described in this video.