Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website http://www.jocmr.org

Review

Volume 7, Number 10, October 2015, pages 742-751

Aurora Kinases and Potential Medical Applications of Aurora Kinase Inhibitors: A Review

Figure

Figure 1.
Figure 1. AKs contain mainly two domains: 1) NH2-terminal regulatory domain (white), 2) COOH-terminal catalytic domain (yellow). The three auroras A, B, and C share great homology in the catalytic domain. Phosphorylation at threonine within the activation loop is necessary for kinase activity.

Table

Table 1. Potential Oncological Applications
 
Aurora kinase inhibitorsTargetsOncological applications
TozasertibAurora A, B and CFirst AKI in clinical use, simultaneous and successive treatment in CML and ALL
PHA-739358 (danusertib)Aurora A, B, C TrKA-a, Ret, FGRPhase II in prostate cancer, in combination use with sorafenib in HCC, phase II in multiple myeloma
CYC116Selective effect on aurora A, B, inhibition of angiogenesisIn combined use with ionizing radiation on ras-mutated colorectal adenocarcinoma, phase II in solid tumors
SNS-314Pan-aurora kinase inhibitorPreclinical studies of cell lines and murine models of prostate, colon and breast cancers, phase I in solid tumors
AMG-900Pan-aurora kinase inhibitorPreclinical studies of hematological and solid tumors
VE-465Pan-aurora kinase inhibitorAntineoplastic activity in preclinical studies of HCC, ovarian cancer and hematologic malignancies
AS703569/R-763Aurora A, B, C FLT1, FLT3, Abl, Akt, VEGFR3Anticancer activity in cell culture in cell culture and murine xenograft models of hemopoietic and solid tumors
PF-03814735Aurora A, B, C, FGFR1, FAK, TrKA, FLT1, METPhase I for solid tumors
AT9283Aurora A, B, Abl, JAK3, T3151 BCR-ABL, wild-type BCR-ABLPreclinical efficacy in hematologic malignancies
GSK1070916Aurora B-INCEP, C-INCEP, SIK, FLT1, FGFR1, FLT4In vivo efficacy in xenograft models, phase I in solid tumors
MLN8054Selective inhibitor of AURKAWithdrawn from clinical use due to sever somnolence and central nervous system toxicity
MLN8237Aurora A, B, T3151 BCR-ABLSeven ongoing phase II studies, one phase III recruiting patients