LY2784544,JAK2inhibitor

Biological Activity:

LY2784544 is highly potent and selective mutant JAK2 (V617F) inhibitor with an IC₅₀ of ~55 nM. It also inhibits IL-3-activated wild type JAK2 with an IC₅₀ of 2.26 μM. Similarly in the proliferation assay, LY2784544 shows anti-proliferative activity in JAK2 V617F-driven cells with an IC₅₀ of 68 nM, compared to 1.36 μM in wild type JAK2-driven cells and 0.94 μM in JAK3-driven cells. LY2784544 significantly inhibits STAT5 phosphorylation in JAK2-V617F Ba/F3 xenografts. Currently LY2784544 is being investigated in a clinical trial for the treatment of essential thrombocythemia, polycythemia vera, and primary myelofibrosis.

How to Use:

• In vitro:  LY2784544 was used at 5-10 µM final concentration in vitro and in cellular assays.
• In vivo:  LY2784544 significantly inhibits STAT5 phosphorylation in JAK2-V617F Ba/F3 xenografts with a Threshold Effective Dose 50 (TED50) of 12.7 mg/kg. LY2784544 also reduces JAK2-V617F Ba/F3 tumor burden in the JAK2-V617F-induced MPN model with a TED50 of 13.7 mg/kg after oral treatment. LY2784544 has no effect on CD71/Ter119 positive erythroid progenitors in spleens of SCID mice after oral treatment.

Reference:

• 1. Srdan Verstovsek . Phase I Study of the JAK2 V617F Inhibitor, LY2784544, in Patients with Myelofibrosis (MF), Polycythemia Vera (PV), and Essential Thrombocythemia (ET). (2011) 53rd ASH Annual Meeting and Exposition.
• 2. Liandong Ma. Efficacy of LY2784544, a Small Molecule Inhibitor Selective for Mutant JAK2 Kinase, In JAK2 V617F-Induced Hematologic Malignancy Models. (2011) 53rd ASH Annual Meeting and Exposition.
• 3. David Mitchell, et al. Development and a Practical Synthesis of the JAK2 Inhibitor LY2784544. (2012) Org. Process Res. Dev., 16 (1), pp 70–81

Products are for research use only. Not for human use.