MCL1

MCL1, a highly regulated member of the BCL2 family, is frequently found to be amplified or overexpressed in both solid tumors and hematologic cancers. It is induced by a wide range of survival signals and rapidly downregulated during apoptosis. Inhibition of MCL1 expression and/or function is therefore of considerable therapeutic interest in cancer, as it is thought to mediate cancer cell survival in myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin’s lymphoma, and multiple myeloma. Small molecule MCL1 inhibitors have been shown to be efficacious as monotherapy in preclinical models of multiple myeloma, acute myeloid leukemia, CLL, and lymphoma.

mcl1-graphic-1

Prelude compounds are competitive inhibitors of BIM binding

PRT1419

Prelude is developing PRT1419, which is designed to be a potent and selective inhibitor of MCL1. An intravenous formulation (IV) is being evaluated in patients with hematological malignancies. Prelude has prioritized development of the IV formulation, which has demonstrated a desirable pharmacokinetic, pharmacodynamic and safety profile with potential for differentiation from competitor compounds in development.