AMG900

ATP-competitive inhibitor of AURKA, AURKB, AURKC

Structure

Information

  • AURKA
  • AURKB
  • AURKC
  • ATP-competitive inhibitor
  • Up to 100 nM

In Vitro Validations

Uniprot ID: O14965
Target Class: Kinase
Target SubClass: cell cycle-regulated kinase
Potency: IC 50
Potency Value: 5 nM
Potency Assay: enzyme inhibition assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Aurora kinase A, STK6, STK15, IAK1, BTAK, AYK1, AU ...

DOI Reference: 10.1158/0008-5472.CAN-10-3001

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Off Target: MAPK14
Potency end-point : IC 50 53 nM
Potency assay (off target): AMG900 was tested in enzyme inhibition assays and ATP-competitive binding assays (Ambit Biosciences).
Probe Selectivity in Vitro:
IC50s are from enzyme inhibition assays. In ATP-competitive binding assays, AMG900 had KD < 50 nM for the Aurora kinases, DDR1, DDR2, and LTKR. (TYK2 IC50 = 220 nM, JNK2 IC50 = 520 nM, MET IC50 = 550 nM, TIE2 IC50 = 650 nM)
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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

AMG900 is an orally available, small molecule, ATP-competitive, low single-digit nM, pan-Aurora-kinase inhibitor (AKI). It shows at least 10-fold in vitro selectivity compared with relevant Janus kinase family members, and among other targets including MET, p38, and TIE2. It has shown activity in more than three dozen cell lines, shows time-dependent activity, and is effective in cell lines resistant to antimitotics such as paclitaxel and to other AKIs, alone or with microtubule-targeting agents. Combination therapy with HDAC inhibitors and low doses of AMG900 shows promise. Histone H3 phosphorylation is a useful biomarker.

(last updated: 29 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

AMG900 is a potent pan Aurora inhibitor that is active in tumor cell lines irrespective of P-gp or BCRP status. Compound is orally bioavailable in mice, rats, dogs and monkeys.

(last updated: 31 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

AMG900 is a potent ATP-competitive inhibitor of Aurora kinases. It exhibits low nanomolar affinity for Aurora kinases (A, B, and C); it also has low nanomolar affinity for DDR1, 10-100 nanomolar affinity for DDR2, LTK, FES, and TIE, and 100-200 nanomolar affinity for 5 additional kinases. It is cell permeable (with low nanomolar potency) and orally bioavailable. AMG900 inhibits Aurora kinase autophosphorylation in cells and the phosphorylation of the Aurora kinase substrate histone H3 in a dose-dependent manner. It inhibits the proliferation of 26 tumor cell lines, including cell lines that are resistant to paclitaxel and other Aurora kinase inhibitors. For the purpose of interrogating Aurora kinase function specifically, it might be important to test alongside other Aurora kinases inhibitors with different off-target profiles.

(last updated: 26 Dec 2016 )