Discovery and Optimization of First-in-Class Molecular Glue Degraders of the WIZ Transcription Factor for Fetal Hemoglobin Induction to Treat Sickle Cell Disease

Kerrigan, John Ryan; Thomsen, Noel M.; Cernijenko, Artiom; Kochanek, Sarah E.; Dewhurst, Janetta; O’Brien, Gary; Ware, Nathaniel F.; Sanchez, Carina C.; Manning, James R.; Ma, Xiaolei; Ornelas, Elizabeth; Savage, Nikolas A.; Partridge, James R.; Patterson, Andrew W.; Lam, Philip; Dales, Natalie A.; Bonazzi, Simone; Borikar, Sneha; Hinman, Amelia E.; Ting, Pamela Y.

doi:10.1021/acs.jmedchem.4c02251

Discovery and Optimization of First-in-Class Molecular Glue Degraders of the WIZ Transcription Factor for Fetal Hemoglobin Induction to Treat Sickle Cell Disease

Sickle cell disease (SCD) is a prevalent, life-threatening condition with few treatment options, attributed to a heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) with small molecules has been pursued as a treatment to ameliorate many disease complications but wi…