Brief Description

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.
IC50 value: 3 nM
Target: JAK2
in vitro: 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.
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.

Solubility

DMSO ≥91mg/mL Water <1.2mg/mL Ethanol ≥8.8mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid