ART0380 + irinotecan

ART0380 + irinotecan is a combination regimen of two drugs, **ART0380**, an orally administered selective small molecule inhibitor of **ataxia telangiectasia and Rad3-related protein** (ATR), combined with **irinotecan**, a topoisomerase I poison and established chemotherapy agent. ART0380 prevents cancer cells from repairing DNA damage by inhibiting ATR, which is a key kinase activated in response to replication stress and DNA damage. Irinotecan further induces replication stress and DNA damage. The synergy of these drugs is especially exploited in tumors with deficiencies in ATR's counterpart, ATM (ataxia-telangiectasia mutated), which are less able to compensate for this dual mechanism, leading to cancer cell death. The combination is currently being evaluated in advanced/metastatic solid tumors—particularly ATM-deficient/ATM-negative cancers such as pancreatic and colorectal cancer— and has shown robust anti-tumor activity and tolerability in clinical studies. ART0380 was discovered via a collaboration between ShangPharma and University of Texas MD Anderson Cancer Center, and is in-licensed and further developed by Artios Pharma[1][2][3][4].