LY2784544

名称和标识

IUPAC标准名

N-{3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-yl}-3-methyl-1H-pyrazol-5-amine

IUPAC传统名

N-{3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-yl}-5-methyl-2H-pyrazol-3-amine

别名

LY2784544

数据登录号

CAS号

1229236-86-5

化合物性质

药理学性质

作用靶点

JAK

安全信息

保存条件

-20°C

产品相关信息

成盐信息

Free Base

描述信息

Research Area

Description

Myeloproliferative disorders

Biological Activity

Description

LY2784544 is selective to V617F mutant JAK2 with IC50 of 55 nM in Ba/F3 cells.

Targets

JAK2 V617F mutant

IC₅₀

55 nM ^[1]

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. ^[1]

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. ^[1]

Clinical Trials

Currently in Phase I clinical trial in patients with JAK2 V617F-positive myeloproliferative disorders.

Features