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 (Synonyms  MK-0457;VX-680;MK0457;VX680;VX 680;MK 0457)
639089-54-6  Technical Data: Price and Availability of  Cas No:639089-54-6

Cas : 639089-54-6 M.Wt: 464.59
Cas : 639089-54-6 Formula: C23H28N8OS
Cas : 639089-54-6 Purity: >98 %
Cas : 639089-54-6 Storage: at 20℃ 2 years
Cas : 639089-54-6 Solubility: 10 mM in DMSO
Cas : 639089-54-6 Name: Tozasertib
50mg/$60 In-stock
100mg/$100 In-stock
250mg/$200 In-stock
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639089-54-6  Data Sheet:
Introduction of 639089-54-6 :
Tozasertib (MK-0457; VX-680) is the inhibitor of Aurora-A, -B, -C kinases with Ki values of 0.6, 18, 4.6 nM respectively. IC50 Value: 0.6 nM(Ki for Aurora A); 18 nM (Ki for Aurora B); 4.6 nM (Ki for Aurora C) Target: Aurora Kinase in vitro: VX-680 induces similar cytotoxicity with IC50 of approximately 300 nM and exhibits an AUR B-like inhibitory phenotype of G2/M arrest, endoreduplication and apoptosis in BaF3 cells transfected with ABL or FLT-3 (mutant and wild type) kinases. VX-680 prevents the CAL-62 proliferation in a time-dependent manner. VX-680 treatment for 14 days significantly decreases the number and size of colonies by approximately 70% in the 8305C and 90% in the CAL-62, 8505C and BHT-101. Treatment of the different ATC cells with VX-680 inhibits proliferation with the IC50 between 25 and 150 ?nM. The VX-680 significantly impairs the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity indicates that VX-680 induces apoptosis in the different cell lines. CAL-62 cells exposed for 12? hours to VX-680 showed an accumulation of cells with ≥4N DNA content. Time-lapse analysis demonstrates that VX-680-treated CAL-62 cells exit metaphase without dividing. Moreover, histone H3 phosphorylation is abrogated following VX-680 treatment. VX-680 has significant inhibitory activity against BCR-Abl bearing the T315I mutation in patient-derived samples. in vivo: VX-680 gives rise to a marked decrease in tumor size in a human AML (HL-60) xenograft model. In mude mice treateed with VX-680 at 75 mg/kg, twice a day intraperitoneally (b.i.d. i.p.) for 13 days, mean tumor volumes are reduced by 98%. Tumor growth decrease is dose dependent and significant at a dose of 12.5 mg/kg b.i.d. VX-680 is well tolerated, with a small decrease in body weight observed only at the highest dose. VX-680 also triggers tumor regresson in pancreatic and colon xenograft models. VX-680 also displays potent antitumor activity when infused i.v. in mude rats bearing established HCT116 tumors. A higher dose of VX-680 (2 mg/kg/h) improves efficacy with a 56% decrease in mean tumor volume.
References on 639089-54-6 :

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