Publications by authors named "John R Kerrigan"

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 with limited success. Herein, we report the discovery of , a novel, potent, and selective molecular glue degrader of the transcription factor WIZ that robustly induces HbF expression as a potential treatment for SCD.

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Article Synopsis
  • - Sickle cell disease (SCD) is a serious inherited condition caused by a mutation in the β-hemoglobin gene, and increasing fetal hemoglobin (HbF) levels can help reduce complications.
  • - Researchers discovered two small molecules, dWIZ-1 and dWIZ-2, that act as molecular glue degraders to induce HbF by targeting a previously unrecognized repressor, the WIZ transcription factor.
  • - These compounds effectively triggered HbF production in animal models, suggesting that targeting WIZ for degradation offers a promising and accessible new treatment approach for SCD.
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We outline a strategy to enable non-directed Pd(II)-catalyzed C-H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C-H acetoxylation reactions, addition of a variety of -containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest.

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