DMPK Strategy for Irreversible Covalent Inhibitor to Guide the Translation From Preclinical to Human

  • DCN1, a novel target for fetal hemoglobin induction for Sickle cell disease, was discovered by the innovative transcriptomic platform at Cellarity
  • Covalent inhibition of DCN1 was designed to achieve the desired pharmacology
  • Developing IVIVE strategy to predict human clearance of covalent inhibitors and applying target turnover informed PK/PD model for predicting human efficacious dose
  • Integrating PK/PD modeling with target occupancy data to guide the translation from preclinical models to human