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Pacritinib

Pacritinib (INN) is a macrocyclic Janus kinase inhibitor that is being developed for the treatment of myelofibrosis. It mainly inhibits Janus kinase 2 (JAK2) and Fms-like tyrosine kinase 3 (FLT3). The drug was in Phase III clinical trials as of 2013. The drug was discovered in Singapore at the labs of S*BIO Pte Ltd. It is a potent JAK2 inhibitor with activity of IC50 = 23 nM for the JAK2WT variant and 19 nM for JAK2V617F with very good selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively).The drug was acquired by Cell Therapeutics, Inc. (CTI) and Baxter International and could effectively address an unmet medical need for patients living with myelofibrosis who face treatment-emergent thrombocytopenia on marketed JAK inhibitors. When Shire Pharmaceuticals purchased Baxalta, a spin-off of Baxter Pharmaceuticals, they halted the development of the drug and ended their partnership with CTI.The drug was given fast-track status in 2014.
In 2016, the FDA placed a full clinical hold on pacritinib due to concerns about increased mortality in patients receiving the drug in the "PERSIST-2" trial. The clinical hold was lifted in January 2017.

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