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Updated: May 28, 2026

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced

H-T Arkenau1, R Plummer2, L R Molife1

  • 1Drug Development Unit, Royal Marsden NHS Foundation Trust, Surrey, London.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|October 22, 2011
PubMed
Abstract

Insights

AT9283, an aurora kinase inhibitor, showed antitumor potential in early trials. This phase I study found it well-tolerated up to 27 mg/m(2)/72 h, with preliminary efficacy in advanced cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • AT9283 is an inhibitor of aurora kinases A and B.
  • It has demonstrated antitumor activity in preclinical models.

Purpose of the Study:

  • To assess the safety and tolerability of AT9283 in a First in Human phase I study.
  • To evaluate pharmacokinetic and pharmacodynamic properties.
  • To determine preliminary efficacy of AT9283 in patients with advanced tumors.

Main Methods:

  • Patients received AT9283 via continuous central venous infusion over 3 days.
  • Dose escalation cohorts were used, starting at 1.5 mg/m(2)/day.
  • Oral bioavailability was assessed, and pharmacodynamic biomarkers were analyzed.

Main Results:

  • AT9283 was generally well tolerated, with dose-related myelosuppression and gastrointestinal issues as main toxicities.
  • The maximum tolerated dose (MTD) was established at 27 mg/m(2)/72 h.
  • Preliminary efficacy was observed, with four patients achieving RECIST stable disease for ≥ 6 months.

Conclusions:

  • AT9283 is well tolerated up to the MTD of 27 mg/m(2)/72 h.
  • Pharmacodynamic analyses indicated antiproliferative and apoptotic activity.
  • AT9283 is currently being evaluated in phase II trials.

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