| Identification | Back Directory | [Name]
Tozasertib | [CAS]
639089-54-6 | [Synonyms]
VX 680
VX-860
MK 0457
Tozasertib
L-001281814
VX-680/MK-0457
Tozasertib/VX-680
VX-680(Tozasertib)
MK-0457,Tozasertib
tozasertib (MK-0457)
Tozasertib Free Base
Tozasertib￡VX680￡MK0457
Tozasertib(MK-0457,VX-680)
VX-680 (MK-0457)(Tozasertib)
VX-680 (Tozasertib, MK-0457)
N-(4-(4-(5-Methyl-1H-pyrazol-3-ylamino)-6-(1-methylpiperidin-4-ylamino)pyrimidin-2-ylthio)phen
N-(4-(4-(5-methyl-1H-pyrazol-3-ylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide
N-(4-(4-(3-methyl-1H-pyrazol-5-ylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide
N-[4-[[4-(4-Methylpiperazin-1-yl)-6-[(5-Methyl-1H-pyrazol-3-yl)aMino]pyriMidin-2-yl]thio]phenyl]cyclopropanecarboxaMide
N-[4-[[4-(4-Methyl-1-piperazinyl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]thio]phenyl]cyclopropanecarboxamide
N-(4-(4-(5-methyl-1H-pyrazol-3-ylamino)-6-(1-methylpiperidin-4-ylamino)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide
Cyclopropanecarboxamide, N-(4-((4-(4-methyl-1-piperazinyl)-6-((5-methyl-1H-pyrazol-3-yl)amino)-2-pyrimidinyl)thio)phenyl)-
Cyclopropanecarboxylic acid N-(4-((4-(4-methylpiperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)pyrimidin-2-yl)sulfanyl)phenyl)amide
Cyclopropane carboxylic acid {4-[4-(4-methyl-piperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino) -pyrimidin-2ylsulphanyl]-phenyl}-amide
Tozasertib
N-[4-[[4-(4-Methyl-1-piperazinyl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]thio]phenyl]cyclopropanecarboxamide | [Molecular Formula]
C23H28N8OS | [MDL Number]
MFCD23726649 | [MOL File]
639089-54-6.mol | [Molecular Weight]
464.59 |
| Chemical Properties | Back Directory | [Melting point ]
248-253°C (dec.) | [density ]
1.40±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Soluble in DMSO (up to 100 mg/ml). | [form ]
powder | [pka]
14.09±0.70(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months. |
| Hazard Information | Back Directory | [Chemical Properties]
White Solid | [Uses]
A multikinase inhibitor once used for cancer treatment. | [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.1 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).2 It shows selectivity against a panel of more than 190 different protein kinases.2 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.1 By depleting Aurora activity, MK-0457 disrupts bipolar spindle formation during mitosis, arresting cell cycle progression at the G2/M phase.1 | [Definition]
ChEBI: N-[4-[[4-(4-methyl-1-piperazinyl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]-2-pyrimidinyl]thio]phenyl]cyclopropanecarboxamide is a N-arylpiperazine. | [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 |
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