| Identification | Back Directory | [Name]
CHZ868 | [CAS]
1895895-38-1 | [Synonyms]
CHZ868
CHZ 868; CHZ-868
Acetamide, N-[4-[[2-[(2,4-difluorophenyl)amino]-1,4-dimethyl-1H-benzimidazol-5-yl]oxy]-2-pyridinyl]- | [Molecular Formula]
C22H19F2N5O2 | [MDL Number]
MFCD30533612 | [MOL File]
1895895-38-1.mol | [Molecular Weight]
423.42 |
| Chemical Properties | Back Directory | [density ]
1.37±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:100.0(Max Conc. mg/mL);236.17(Max Conc. mM) | [form ]
Solid | [pka]
13.27±0.70(Predicted) | [color ]
White to gray |
| Hazard Information | Back Directory | [Uses]
CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell. | [Definition]
ChEBI: CHZ868 is a memger of the class of benzimidazoles that is benzimidazole that is substituted by methyl groups at positions 1 and 4, by a 2,4-difluoroanilino group at position 2, and by a (2-acetamidopyridin-4-yl)oxy group at position 5. It is a type II JAK2 inhibitor with antineoplastic activity. It has a role as an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor and an antineoplastic agent. It is a member of benzimidazoles, a member of acetamides, a member of pyridines, a difluorobenzene, an aromatic ether, a secondary amino compound and an aromatic amine. | [Biological Activity]
Orally activetype II tyrosine kinase I inhibitor against VEGFR1/2 (FLT1/KDR)PDGFR1/2KITand ROS1 oncogenic fusions/mutations-drivent growth.
CHZ868 is a type II tyrosine kinase inhibitor th at exhibits potent antiproliferation activity against VEGFR1/2 (FLT1/KDR)PDGFR1/2KITand ROS1 TEL fusions-as well as JAK2 V617Fbut not RAF V600Emutation-driven oncogenic growth (IC50 = 2/114/23164051 against respective BaF3 transformants) via stablizing target kinases in the inactive “DFG-out” conformation. CHZ868 overcomes Type I JAK inhibitor resistance of JAK2/MPN mutant MPN and JAK2 I682F/CRLF2-rearranged B-ALL cells both in cultures and in mice in vivo (30-40 mg/kg/day p.o.). Comparing to BBT594CHZ868 is ineffective against BCR-ABLTEL-FLT3TEL-RET. | [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]. | [IC 50]
JAK2: 110 nM (IC50) | [storage]
Store at -20°C | [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. DOI:10.1016/j.ccell.2015.06.006
[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. DOI:10.1016/j.ccell.2015.06.005 |
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| Company Name: |
Twochem Co.Ltd.
|
| Telephone: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
| Company Name: |
cjbscvictory
|
| Telephone: |
13348960310 13348960310 |
| Website: |
www.weikeqi-biotech.com/ |
| Company Name: |
ChemeGen
|
| Telephone: |
18818260767 |
| Website: |
https://www.chemegen.com |
| Company Name: |
Bide Pharmatech Ltd.
|
| Telephone: |
400-1647117 13681763483 |
| Website: |
https://www.bidepharm.com/ |
|