Mechanism of action: ATR serine/threonine kinase inhibitor

Preclinical pharmacology

AZ20 is a potent inhibitor of ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 4.5nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumour cells with an IC50 of 50 nMATR. AZ20 is orally bioavailable mouse, rat and dog with unbound mouse plasma Cmax = 0.86 µM ±0.12 @ 50mg/kg PO, 2h. The CNS exposure is unknown.

LoVo single agent activity: 78% TGI p <0.0005 d 21 (50mg/kg QD or 25mg/kg BD PO, 2-weeks), ≤10% body weight loss.

Additional Information

Publications for this compound

Find out more about this compound by reading related Publications:

Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity.

Gene information from the NCBi

This compound works on the following genes: