product name Gandotinib (LY2784544)
Description: Gandotinib, also known as LY2784544, is a potent and selective JAK2 inhibitor with IC50 of 3 nM, it is effective in JAK2V617F, 8- and 20-fold selective versus JAK1 and JAK3. Gandotinib effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In vivo, Gandotinib effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP ascitic tumor cells and significantly reduced Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model.
References: Blood Cancer J. 2013 Apr 12;3:e109.
469.94
Formula
C23H25ClFN7O
CAS No.
1229236-86-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 94 mg/mL (200.0 mM)
Water: <1 mg/mL
Ethanol: 9 mg/mL (19.1 mM)
Solubility (In vivo)
Synonyms
LY2784544
other peoduct :
| In Vitro |
In vitro activity: 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. Though biochemical assays do not reveal selectivity of LY2784544 for mutant JAK2V617F, LY2784544 shows higher selectivity for inhibition of JAK2-mediated signaling and induction of apoptosis in Ba/F3 cells expressing JAK2V617F than wild-type cells. Kinase Assay: LY2784544(gandotinib) is a potent JAK2 inhibitor with IC50 of 3 nM, effective in JAK2V617F(Ki=0.245 nM), 8- and 20-fold selective versus JAK1 and JAK3. Cell Assay: LY2784544 showed minimal inhibition of STAT5 phosphorylation at 50 and 200 nM concentrations in IL-3-stimulated Ba/F3 cells which express wild-type JAK2. LY2784544 significantly inhibited the cell proliferation of JAK2V617F-expressing cells with IC50 ＝55 nM. In JAK2V617F-expressing cells, LY2784544 induced apoptosis with EC50±s.d.of 113±0.023 nM measured by Caspase3/7-glo assays. |
|---|---|
| In Vivo | 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. |
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| Formulation & Dosage | |
| References | Blood Cancer J. 2013 Apr 12;3:e109. |
