Pacritinib (Vonjo)

Mechanism of action

From the NCI Drug Dictionary: An orally bioavailable inhibitor of Janus kinase 2 (JAK2) and the JAK2 mutant JAK2V617F with potential antineoplastic activity. Pacritinib competes with JAK2 for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and so caspase-dependent apoptosis. Also, per Hart et al. 2011 pacritinib is a tyrosine kinase inhibitor (TKI) with equipotent activity against FLT3 (IC50=22 n) and Janus kinase 2 (JAK2, IC50=23 n).

Preliminary data

Myelofibrosis

1. Komrokji RS, Seymour JF, Roberts AW, Wadleigh M, To LB, Scherber R, Turba E, Dorr A, Zhu J, Wang L, Granston T, Campbell MS, Mesa RA. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Blood. 2015 Apr 23;125(17):2649-55. Epub 2015 Mar 11. link to original article PubMed