| Molecular Weight: | 469.94 |
| Formula: | C23H25ClFN7O |
| Purity: | ≥ 98% |
| CAS#: | 1229236-86-5 |
| Solubility: | DMSO up to 100 mM |
| Chemical Name: | 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine |
| Storage: | Powder:4oC 1 year. DMSO:4oC3 month;-20oC 1 year. |
Biological Activity:
LY2784544 is highly potent and selective mutant JAK2 (V617F) inhibitor with an IC50of ~55 nM. It also inhibits IL-3-activated wild type JAK2 with an IC50of 2.26 μM. Similarly in the proliferation assay, LY2784544 shows anti-proliferative activity in JAK2 V617F-driven cells with an IC50of 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
LY2784544_spec.pdf
LY2784544_MSDS.pdf
Products are for research use only. Not for human use.
