Structural highlights
Function
A4TVL0_9PROT
Publication Abstract from PubMed
Aberrant activation of the JAK-STAT signaling pathway has been implicated in the pathogenesis of a range of hematological malignancies and autoimmune disorders. Here we describe the design, synthesis, and characterization of JAK2/3 PROTACs utilizing a phenyl glutarimide (PG) ligand as the cereblon (CRBN) recruiter. SJ10542 displayed high selectivity over GSPT1 and other members of the JAK family and potency in patient-derived ALL cells containing both JAK2 fusions and CRLF2 rearrangements.
Development of Potent and Selective Janus Kinase 2/3 Directing PG-PROTACs.,Alcock LJ, Chang Y, Jarusiewicz JA, Actis M, Nithianantham S, Mayasundari A, Min J, Maxwell D, Hunt J, Smart B, Yang JJ, Nishiguchi G, Fischer M, Mullighan CG, Rankovic Z ACS Med Chem Lett. 2022 Feb 21;13(3):475-482. doi:, 10.1021/acsmedchemlett.1c00650. eCollection 2022 Mar 10. PMID:35300081[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alcock LJ, Chang Y, Jarusiewicz JA, Actis M, Nithianantham S, Mayasundari A, Min J, Maxwell D, Hunt J, Smart B, Yang JJ, Nishiguchi G, Fischer M, Mullighan CG, Rankovic Z. Development of Potent and Selective Janus Kinase 2/3 Directing PG-PROTACs. ACS Med Chem Lett. 2022 Feb 21;13(3):475-482. PMID:35300081 doi:10.1021/acsmedchemlett.1c00650
