CHR-6494 Chemical Properties

Density 

1.39±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble5mg/mL, clear (warmed)

pka

13.24±0.40(Predicted)

form 

powder

color 

white to beige

InChI

1S/C16H16N6.C2HF3O2/c1-2-7-17-15-5-6-16-18-10-14(22(16)21-15)11-3-4-13-12(8-11)9-19-20-13;3-2(4,5)1(6)7/h3-6,8-10H,2,7H2,1H3,(H,17,21)(H,19,20);(H,6,7)

InChIKey

ILWYDZNXJQESDI-UHFFFAOYSA-N

SMILES

OC(=O)C(F)(F)F.CCCNc1ccc2ncc(-c3ccc4[nH]ncc4c3)n2n1

Safety Information

WGK Germany 

3

Storage Class

11 - Combustible Solids

CHR-6494 Usage And Synthesis

Description

CHR-6494 is a haspin protein kinase inhibitor (IC₅₀ = 2 nM) selective over 27 other protein kinases, including Aurora B kinase (IC₅₀ > 1 μM). Haspin is a kinase necessary for mitosis that selectively phosphorylates histone 3 at the threonine 3 residue (H3T3ph). CHR-6494 decreases phosphorylation of H3T3 and arrests the cell cycle in the G₂/M phase, which leads to apoptosis. It showed promising results in a xenograft tumor model.

Uses

CHR6494 is a small-molecule inhibitor of histone kinase haspin, with a wide spectrum of anticancer effects.

General Description

A cell-permeable indazolylimidazopyridazinamine compound that acts as a potent and reversible inhibitor of histone kinase haspin activity (IC₅₀ = 2 nM) with moderate selectivity over TrkA, GSK-3β, PIM1, Cdk1/B and Cdk2/A (% inhibition at 100 nM = 58, 48, 36, 34 and 33, respectively) among a panel of 27-kinases. Shown to block pH3-Thr³, with no effect on pH3-Ser¹⁰ and pH3-Ser²⁸, cause mitotic catastrophe, upregulate BUB1 and cyclin B1 levels, and potently induce apoptosis (IC₅₀ = 473, 500 and 752 nM in HeLa, HCT-116 and MDA-MB-231 cells, respectively). Further, efficiently blocks bFGF-induced sprouting vessel by 70% at 1 μM (chicken embryo aortic arch ring assay) and suppresses tumor growth in HCT-116 xenografted mouse model (50 mg/kg, i.p.).

References

[1] D HUERTAS. Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin[J]. Oncogene, 2011, 31 11: 1408-1418. DOI: 10.1038/onc.2011.335

CHR-6494(1333377-65-3)Related Product Information

• N-PROPYLBENZENE
• Trichloropropylsilane