Research Area
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Description
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Myeloproliferative disorders |
Biological Activity
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Description
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LY2784544 is selective to V617F mutant JAK2 with IC50 of 55 nM in Ba/F3 cells. |
Targets
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JAK2 V617F mutant |
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IC50 |
55 nM [1] |
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In Vitro
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LY2784544 also inhibits IL-3-activated wild type JAK2 with IC50 of 2.26 μM. Similarly in the proliferation assay, LY2784544 shows antiproliferation activity in JAK2 V617F-driven cells with IC50 of 68 nM, compared to 1.36 μM in wild type JAK2-driven cells and 0.94 μM in JAK3-driven cells. [1] |
In Vivo
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LY2784544 significantly inhibits STAT5 phosphorylation in Ba/F3-JAK2 V617F-GFP xenografts with a Threshold Effective Dose 50 (TED50) of 12.7 mg/kg. LY2784544 also reduces Ba/F3-JAK2 V617F-GFP 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. [1] |
Clinical Trials
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Currently in Phase I clinical trial in patients with JAK2 V617F-positive myeloproliferative disorders. |
Features
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