DC Chemicals Limited
China
Product Name: CHZ868
Price: $450.0/100mg $900.0/250mg $1800.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

1895895-38-1

1895895-38-1 structure

1895895-38-1 structure

Name: CHZ868
Chemical Name: CHZ868
CAS Number: 1895895-38-1
Molecular Formula: C₂₂H₁₉F₂N₅O₂
Molecular Weight: 423.415
Catalog: Signaling Pathways Epigenetics JAK
Create Date: 2018-02-07 14:11:01
Modify Date: 2024-01-03 15:36:39
CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

Name	CHZ868
Synonyms	CHZ868 Acetamide, N-[4-[[2-[(2,4-difluorophenyl)amino]-1,4-dimethyl-1H-benzimidazol-5-yl]oxy]-2-pyridinyl]- N-[4-({2-[(2,4-Difluorophenyl)amino]-1,4-dimethyl-1H-benzimidazol-5-yl}oxy)-2-pyridinyl]acetamide

Description	CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.
Related Catalog	Signaling Pathways >> Epigenetics >> JAK Signaling Pathways >> JAK/STAT Signaling >> JAK Signaling Pathways >> Stem Cell/Wnt >> JAK Research Areas >> Cancer
Target	JAK2:110 nM (IC50)
In Vitro	CHZ868 potently inhibits constitutive JAK2 and STAT5 phosphorylation in JAK2V617F SET2 cells. CHZ868 potently inhibits the proliferation of SET2 cells (GI50=59nM), and has 6-fold less growth inhibitory activity against CMK cells (GI50=378nM)[1]. At 100 nM CHZ868 has activity against 26 kinases, including JAK2 and TYK2. CHZ868 is thought to engage with the hinge region of JAK2 through two H-bonds, formed between the amino-pyridine of CHZ868 and the backbone-NH/CO of L932, while the pyridine is occupying the adenine pocket of the ATP binding site. CHZ868 potently suppresses the growth of CRLF2-rearranged human B-ALL cells, abrogates JAK2 signaling[2].
In Vivo	CHZ868 is characterized by high passive permeability, good metabolic stability, and low water solubility, as well as by moderate blood clearance and good oral bioavailability, making it suitable for in vivo use. CHZ868 improves survival in mice with human or murine B-ALL. CHZ868 and dexamethasone synergistically induces apoptosis in JAK2-dependent B-ALLs and further improves survival compared to CHZ868 alone[2].
Cell Assay	CHZ868 is dissolved in DMSO to make 10 mM stock solution and diluted in culture media. Cells are treated with CHZ868 (0, 0.05, 0.1, 0.2 μM) or vehicle (DMSO). After 48 hr (Ba/F3 cells) or 72 hr (MHH-CALL4 and PDX cells), CellTiter-Glo Luminescent Cell Viability Assay is added (10 μL undiluted or 25 μL of a 1:2 dilution in each well) and plates are read[2].
Animal Admin	Mice: CHZ868 is reconstituted in 0.5% methylcellulose / 0.5% Tween-80 and administered at doses of 10 or 30 mg/kg/day by oral gavage. Pharmacokinetic/pharmacodynamic and efficacy studies in the mouse model of rhEpo-induced polycythemia are carried out essentially as reported. Detection of STAT5 phosphorylation in spleen lysates by Meso Scale Discovery is performed[2].
References	[1]. Meyer SC, et al. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. Cancer Cell. 2015 Jul 13;28(1):15-28. [2]. Wu SC, et al. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13;28(1):29-41.

Density	1.4±0.1 g/cm3
Molecular Formula	C₂₂H₁₉F₂N₅O₂
Molecular Weight	423.415
Exact Mass	423.150696
LogP	5.11
Index of Refraction	1.640
Storage condition	2-8℃