JAK2V617F Inhibitor INCB160058

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable specific pseudokinase (JH2)-binding inhibitor of the Janus-associated kinase 2 (JAK2) mutation JAK2V617F, with potential antineoplastic activity. Upon oral administration, JAK2V617F inhibitor INCB160058 selectively targets and binds to the pseudokinase (JH2) domain of JAK2V617F at the canonical ATP-binding site and inhibits the activation of JAK2V617F and JAK2V617F-mediated signaling. This may result in the inhibition of the JAK-STAT signaling pathway and may induce apoptosis in JAK2V617F-overexpressing cells. The JAK2 mutated form JAK2V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival. It is the most common oncogenic driver in myeloproliferative neoplasms (MPNs). INCB160058 does not inhibit wild-type (WT) JAK2.

**Synonyms:** - INCB 160058 - INCB-160058 - INCB160058 - JH2 Inhibitor INCB160058 - Pseudokinase-targeting Agent INCB160058