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Current Clinical Investigations in Myelofibrosis

The US Food and Drug Administration (FDA) approval of Janus kinase 2 inhibitors, ruxolitinib and fedratinib for the treatment of intermediate-2 or high-risk primary or secondary myelofibrosis (MF) has revolutionized the management of MF. Nevertheless, these drugs do not reliably alter the natural history of disease. Burgeoning understanding of the molecular pathogenesis and the bone marrow microenvironment in MF has galvanized the development of targeted therapeutics. This review provides insight into the novel therapies under clinical evaluation.

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S2736 Fedratinib (TG101348) Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and RET (c-RET) with IC50 of 15 nM and 48 nM, respectively. Fedratinib has potential antineoplastic activity. Fedratinib inhibits proliferation and induces apoptosis. Phase 2.

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FLT3 c-RET Apoptosis related JAK