PRT12396

PRT12396 is a preclinical, mutant-selective small molecule inhibitor targeting the Janus kinase 2 (JAK2) V617F mutation. Developed by Prelude Therapeutics, it specifically targets the JH2 (pseudokinase) domain of the mutant protein. This mechanism allows for the selective inhibition of the V617F mutant form of JAK2, which is the primary driver of various myeloproliferative neoplasms (MPNs), including polycythemia vera and myelofibrosis. By sparing wild-type JAK2, PRT12396 aims to reduce mutant allele burden and modify disease progression while potentially avoiding the hematologic toxicities (such as anemia and thrombocytopenia) often associated with non-selective JAK inhibitors. In November 2025, Incyte Corporation entered into an agreement for an exclusive option to license and further develop the program following the commencement of Phase 1 clinical trials.

Other names

JAK2V617F JH2 inhibitorJAK-2V617F JH2 inhibitorJAK 2V617F JH2 inhibitor