Table 2.

Aurora kinase inhibitors in clinical development

InhibitorTargetAdministrationPhase I DLTBest responseCurrent status
MK-0457 (VX-680; Merck; ref. 31)Aurora A (Ki = 0.66 nmol/L)I.v. (continuous i.v. 5 d every 4 wk)NeutropeniaRemission (leukemia)Phase II
Aurora B (Ki = 18 nmol/L)Stable disease (solid tumors)
Aurora C (Ki = 4.6 nmol/L)
FLT3 (Ki = 30 nmol/L)
BCR-ABL T315I
JAK
AZD1152 (AstraZeneca; ref. 32)Aurora B (Ki = 0.3 nmol/L)I.v. (2 h weekly or continuous i.v. 7 d)NeutropeniaStable disease (solid tumors)Phase II
Aurora C (Ki = 17 nmol/L)
PHA-739358 (Nerviano; ref. 33)Aurora A (IC50 = 27 nmol/L)I.v. (1 d every 2 wk)NeutropeniaStable disease (solid tumors)Phase II
Aurora B (IC50 = 35 nmol/L)
Aurora C (IC50 = 120 nmol/L)
FLT3 (IC50 = 390 nmol/L)
BCR-ABL T315I
MLN8054 (Millennium; ref. 35)Aurora A (IC50 = 5 nmol/L)OralSomnolenceStable disease (solid tumors)Phase I
R763 (Merck/Serono)Aurora BOral and i.v.NANAPhase I
AT9283 (Astex)Aurora A (IC50 < 3 nmol/L)Oral and i.v.NANAPhase I
Aurora B (IC50 < 3 nmol/L)
BCR-ABL T315I
JAK2
CYC116 (Cyclacel)Aurora A/BOralNANAPhase I
VEGFR2
  • Abbreviations: NA, data not available; Ki, dissociation constant for inhibitor binding; JAK, Janus-activated kinase; VEGFR2, vascular endothelial growth factor receptor 2.