CHR-6494 TFA

SKU: orb1940176

Description

CHR-6494 TFA is a potent haspin inhibitor, with an IC50 of 2 nM. It inhibits histone H3T3 phosphorylation. CHR-6494 TFA induces the apoptosis of cancer cells, including melanoma and breast cancer. CHR-6494 TFA can be used in the research of cancer.(In Vitro):Administration of CHR-6494 (TFA; 0-10-5 nM; 72 hours) dose-dependently inhibits the growth of cancer cells, such as HCT-116, HeLa, MDA-MB-231, and Wi-38 cells, with an IC50s of 500 nM, 473 nM, 752 nM and 1059 nM, respectively. Administration of CHR-6494 (TFA; 500 nM) produces a mitotic catastrophe with abnormal morphology of the mitotic spindle and centrosome amplification, and upregulates the spindle assembly checkpoint protein BUB1 and the marker of mitotic arrest cyclin B1.(In Vivo):Administration of CHR-6494 (TFA; 50 mg/kg; i.p. in two cycles of five consecutive days for 15 days) inhibits the growth of tumor and no obvious body weight change is observed in nude mice bearing HCT-116 human colorectal cancer cells.

Key Properties

• CAS Number: 1458630-17-5
• MW: 406.362
• Purity: >98% (HPLC)
• Formula: C₁₈H₁₇F₃N₆O₂
• SMILES: OC(=O)C(F)(F)F.CCCNc1ccc2ncc(-c3ccc4[nH]ncc4c3)n2n1
• Target: DHODH

Bioactivity

• In Vivo:
  CHR-6494 (TFA; 50 mg/kg; i.p. in two cycles of five consecutive days for 15 days) inhibits the growth of tumorin nude mice bearing HCT-116 human colorectal cancer cells. CHR-6494 (TFA; 20 mg/kg; intraperitoneal injection for 15 consecutive days) inhibits the tumor growth in nude mice bearing MDA-MB-231 xenograft tumors. Animal model: Male 4-5 weeks old athymic nu/nu mice harboring HCT-116 cells xenograft tumor with a tumor volume of 200 mm3. Dosage: 50 mg/kg (diluted in a solution of 10% DMSO/20% 2-hydroxypropyl-b-cyclodextrin). Administration: i.p. in two cycles of five consecutive days for 15 days. Result: Dose-dependent tumor growth inhibition was demonstrated. Animal model: 4‐week‐old female nude mice bearing MDA-MB-231 xenograft tumors. Dosage: 20 mg/kg in a final formulation in 10% DMSO/20% 2‐hydroxypropyl‐β‐cyclodextrin. Administration: i.p. for 15 consecutive days. Result: Inhibited the tumor volume and weight compared with the control group in nude mice bearing MDA-MB-231 xenograft tumors. Enhanced the tumor volume and weight inhibition of MLN8237 (20 mg/kg; p.o.) In vivo.
• In Vitro:
  CHR-6494 (TFA; 0-105 nM; 72 hours) dose-dependently inhibits the growth of cancer cells, such as HCT-116, HeLa, MDA-MB-231, and Wi-38 cells, with IC50s of 500 nM, 473 nM, 752 nM and 1059 nM, respectively. CHR-6494 (TFA; 500 nM) produces a mitotic catastrophe with abnormal morphology of the mitotic spindle and centrosome amplification, and upregulates the spindle assembly checkpoint protein BUB1 and the marker of mitotic arrest cyclin B1.CHR-6494 (TFA; 0, 0.5, 1.0 μM; 24 to 36 h) is an inhibitor of angiogenesis in the ex vivo chicken embryo aortic arch ring assay. CHR-6494 (TFA) exhibits inhibitory activities against melanoma cell lines, including BRAFV600E mutants, NRAS mutants, and wild type cells, with IC50s ranging from 396 nM to 1229 nM. CHR-6494 (TFA; 300 nM and 600 nM; 72 hours) induces apoptosis, increases caspase 3/7 activity by 3- and 6-fold, respectively in COLO-792 cells, and to 8.5- and 16-fold in RPMI-7951 melanoma cells. CHR-6494 (TFA; 50, 200 nM; 1 week) enhances the antiproliferative effects of MLN8237 in MDA-MB-231, SKBR3 breast cancer cells. CHR-6494 (TFA; 200 nM; 72 hours) enhances the apoptosis of MDA-MB-231 and SKBR3 cells when combined with MLN8237.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CHR 6494 TFA

Quick Database Links

Gene Symbol

DHODH