Tozasertib
Tozasertib is an anticancer chemotherapeutic pan-aurora kinase (AurK) inhibitor that also inhibits FMS-like tyrosine kinase 3 (FLT3) and Abl. Tozasertib is currently in clinical trials as a potential treatment for acute lymphoblastic leukemia (ALL). In cellular models of cancer, tozasertib activates caspase-3 and PARP and decreases expression of HDAC, increasing apoptosis and inhibiting cell growth. In other cellular models, tozasertib inhibits cell proliferation and metastasis by blocking downstream ERK signaling and downregulating cdc25c and cyclin B. This compound also decreases tumor growth in an in vivo model of prostate cancer.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18977589
| Cas No. |
639089-54-6 |
|---|---|
| Purity |
≥98% |
| Formula |
C23H28N8OS |
| Formula Wt. |
464.59 |
| IUPAC Name |
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide |
| Synonym |
VX680, MK0457 |
| Melting Point |
245-260°C |
| Solubility |
DMSO at 100 mg/mL |
| Appearance |
White to pale yellow powder |
Okabe S, Tauchi T, Tanaka Y, et al. Activity of histone deacetylase inhibitors and an Aurora kinase inhibitor in BCR-ABL-expressing leukemia cells: Combination of HDAC and Aurora inhibitors in BCR-ABL-expressing cells. Cancer Cell Int. 2013 Apr 4;13(1):32. PMID: 23556431.
Li Y, Zhou W, Wei L, et al. The effect of Aurora kinases on cell proliferation, cell cycle regulation and metastasis in renal cell carcinoma. Int J Oncol. 2012 Dec;41(6):2139-49. PMID: 23007526.
Giles FJ, Swords RT, Nagler A, et al. MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia. Leukemia. 2013 Jan;27(1):113-7. PMID: 22772060.
Jeet V, Russell PJ, Verma ND, et al. Targeting aurora kinases: a novel approach to curb the growth & chemoresistance of androgen refractory prostate cancer. Curr Cancer Drug Targets. 2012 Feb;12(2):144-63. PMID: 22229247.
Salah E, Ugochukwu E, Barr AJ, et al. Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. J Med Chem. 2011 Apr 14;54(7):2359-67. PMID: 21417343.
Oliveira TM, Ahmad R, Engh RA. VX680 binding in Aurora A: π-π interactions involving the conserved aromatic amino acid of the flexible glycine-rich loop. J Phys Chem A. 2011 Apr 28;115(16):3895-904. PMID: 21306143.
