639089-54-6 Usage
Description
The Aurora kinases (A, B, and C) are a family of serine-threonine kinases that regulate various stages of mitotic function. With significant roles in cell cycle and cell division, Aurora kinase gene amplification and overexpression are linked to tumorigenesis. MK-0457 is a potent pan-Aurora kinase inhibitor but favors Aurora A (Ki = 0.6 nM) over Aurora B (Ki = 18 nM) or Aurora C (Ki = 4.6 nM). It shows selectivity against a panel of more than 190 different protein kinases. MK-0457 effectively inhibits proliferation of several different cell lines of clear cell renal carcinoma (IC50s = <10 μM) and blocks the growth of tumors in a rodent model of cancer (80 mg/kg), inhibiting histone H3 phosphorylation and increasing apoptosis. By depleting Aurora activity, MK-0457 disrupts bipolar spindle formation during mitosis, arresting cell cycle progression at the G2/M phase.
Chemical Properties
White Solid
Uses
Tozasertib is used as a multikinase inhibitor once used for cancer treatment.
Biochem/physiol Actions
VX-680 is an ATP site-targeting potent aurora kinase inhibitor (Aurara A/B/C Ki(app) = 0.6/18/4.6 nM) that affects FLT3, BCR-Abl, BCR-Abl (T315I), Lck, ITK, Src, and Fyn only at higher concentrations (Ki(app) = 30, 30, 42, 80, 220, 350, 520 nM, respectively) and exhibits little inhibitory potency toward 52 other kinases (Ki(app) >1 μM). VX-680 exhibits potent antiproliferation activity in a wide variety of cancer cultures (IC50 from 15 to 113 nM) as a result of cell cycle arrest and apoptosis induction, as well as causes tumor retardation (by 98% on day 13; 75 mg/kg b.i.d i.p.; HL-60 in mice) and regression (2 mg/kg/h 3 d/wk i.v. infusion; HCT116 in rats) in vivo. Crystallography data reveal a tight association of VX-680 with a hydrophobic pocket present only in a closed, inactive kinase conformation, which forms the basis of its selectivity profile, including its activity toward wild-type and the Imatinib-resistant (T315I) Abl.
References
1) Harrington et al. (2004), VX-680, a potent and selective small molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo; Nat. Med., 10 262
2) Fei et al. (2010), Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias; Mol. Cancer Ther., 9 1318
3) Dewerth et al. (2012), In vitro evaluation of the Aurora kinase inhibitor VX-680 for Hepatoblastoma; Pediatr. Surg. Int., 28 579
Check Digit Verification of cas no
The CAS Registry Mumber 639089-54-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,3,9,0,8 and 9 respectively; the second part has 2 digits, 5 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 639089-54:
(8*6)+(7*3)+(6*9)+(5*0)+(4*8)+(3*9)+(2*5)+(1*4)=196
196 % 10 = 6
So 639089-54-6 is a valid CAS Registry Number.
InChI:InChI=1/C23H28N8OS/c1-15-13-20(29-28-15)25-19-14-21(31-11-9-30(2)10-12-31)27-23(26-19)33-18-7-5-17(6-8-18)24-22(32)16-3-4-16/h5-8,13-14,16H,3-4,9-12H2,1-2H3,(H,24,32)(H2,25,26,27,28,29)
639089-54-6Relevant articles and documents
Kinase inhibition and anticancer therapy
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, (2009/05/29)
This invention relates to novel uses for Compound E in the treatment of diseases, in particular cancer, associated with aberrant kinase expression.
ABL KINASE INHIBITION
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Page/Page column 19, (2008/06/13)
The present invention relates to inhibition of AbI kinase.