Tozasertib (MK-0457, VX-680)

For research purposes only

Cat. No BA120996159

Availability - in stock

Description of biological activity

Selective small-molecule inhibitor of Aurora kinases, VX-680, that blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types. This compound causes profound inhibition of tumor growth in a variety of in vivo xenograft models, leading to regression of leukemia, colon and pancreatic tumors at well-tolerated doses [1]. VX-680 has entered the Phase II clinical trials among patients with myelogenous leukemia and lung cancer.
IC50: 0.61nM (Aurora A Kinase), 30nM (Aurora B Kinase) [2]
Target: Aurora A Kinase, Aurora B Kinase

Therapeutic area

Lung cancer, myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia

Biological target category

Serine-Threonine Protein Kinase

TECHNICAL INFORMATION

cyclopropane carboxylic acid {4-[4-(4-methyl-piperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)-pyrimidin-2-ylsulphanyl]-phenyl}-amide Selective inhibitor of Aurora A Kinase (AURKA)

IUPAC Name: cyclopropane carboxylic acid {4-[4-(4-methyl-piperazin-1-yl)-6-(5-methyl-2H-pyrazol-3-ylamino)-pyrimidin-2-ylsulphanyl]-phenyl}-amide

Chemical Formula: C23H28N8OS

SMILES: CN1CCN(CC1)C1=CC(NC2=CC(C)=NN2)=NC(SC2=CC=C(NC(=O)C3CC3)C=C2)=N1

CAS Number: 639089-54-6

Molecular Weight: 464.590

Purity: > 98% chemical purity (LCMS)

Solubility: 10mM in DMSO

1H-NMR spectrum (click to enlarge)

REFERENCES

[1] Harrington EA, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004 Mar;10(3):262-7

[2] Rawson TE et al. A pentacyclic aurora kinase inhibitor (AKI-001) with high in vivo potency and oral bioavailability. J Med Chem. 2008 Aug 14;51(15):4465-75

[3] EXELIXIS, INC. KINASE MODULATORS AND METHOD OF USE WO2006/74057 A3, 2006

[4]. Nature Medicine, 2004, 10, 262-267

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