Dawn of Aurora kinase inhibitors as anticancer drugs.
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.
Doggrell
Sheila A
SA
Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New Zealand. s.doggrell@xtra.co.nz
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
D000970:Antineoplastic Agents; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001549:Benzamides; D004791:Enzyme Inhibitors; D007211:Indoles; D010879:Piperazines; D017346:Protein Serine-Threonine Kinases; D011799:Quinazolines; D013449:Sulfonamides; C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines; C576918:Aurka protein, mouse; C474723:hesperadin