Abstract
With the current standard chemotherapy regimens only approximately 25% of acute myelogenous leukaemia (AML) patients survive > 5 years. Aurora kinases are overexpressed in many human cancers. VX-680 inhibited Aurora-A, -B, -C and the FMS-like tyrosine kinase-3 with apparent inhibitory constants of 0.6, 18, 4.6 and 30 nM, respectively. In primary leukaemia cells from patients with AML, which were refractory to standard therapies, VX-680 inhibited colony formation. In nude mice, VX-680 markedly reduced human AML tumours. The development of VX-680 for use in AML should continue.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Aurora Kinase A
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Aurora Kinases
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Benzamides / chemistry
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Benzamides / pharmacology*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Humans
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Indoles / chemistry
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Indoles / pharmacology*
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Molecular Structure
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Piperazines / chemistry
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Piperazines / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / pharmacology*
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Quinazolines / chemistry
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Quinazolines / pharmacology*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
Substances
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4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline
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Antineoplastic Agents
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Benzamides
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Enzyme Inhibitors
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Indoles
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Piperazines
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Quinazolines
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Sulfonamides
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tozasertib
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Aurka protein, mouse
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Aurora Kinase A
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Aurora Kinases
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Protein Serine-Threonine Kinases
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hesperadin