7SHH

Bacterial cereblon homologue in complex with (R)-3-(4-methoxyphenyl)piperidine-2,6-dione

Summary for 7SHH

Entry DOI	10.2210/pdb7shh/pdb
Descriptor	Cereblon isoform 4, ZINC ION, (3R)-3-(4-methoxyphenyl)piperidine-2,6-dione, ... (4 entities in total)
Functional Keywords	cereblon, protac, targeted protein degradation, tbd, signaling protein
Biological source	Magnetospirillum gryphiswaldense
Total number of polymer chains	3
Total formula weight	41922.59
Authors	Nithianantham, S.,Fischer, M. (deposition date: 2021-10-08, release date: 2022-04-13, Last modification date: 2024-05-22)
Primary citation	Alcock, L.J.,Chang, Y.,Jarusiewicz, J.A.,Actis, M.,Nithianantham, S.,Mayasundari, A.,Min, J.,Maxwell, D.,Hunt, J.,Smart, B.,Yang, J.J.,Nishiguchi, G.,Fischer, M.,Mullighan, C.G.,Rankovic, Z. Development of Potent and Selective Janus Kinase 2/3 Directing PG-PROTACs. Acs Med.Chem.Lett., 13:475-482, 2022 Cited by PubMed Abstract: 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. PubMed: 35300081 DOI: 10.1021/acsmedchemlett.1c00650 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.9 Å)

Structure validation