A-911

A-911 is a potent, orally bioavailable small molecule antagonist of the 5-HT7 (HTR7) serotonin receptor, developed by AbbVie for cancer immunotherapy. It was identified through medicinal chemistry efforts following the discovery that 5-HT7 signaling in conventional type 1 dendritic cells (cDC1s) within the tumor microenvironment constrains anti-tumor immunity. By antagonizing 5-HT7, A-911 enhances IL-12 production by cDC1s, promotes CD8+ T-cell cross-priming, and increases antigen-specific T-cell killing. In preclinical studies, A-911 demonstrated low brain exposure and was well-tolerated in mice, showing efficacy as a monotherapy and in combination with anti-PD-1 or anti-CTLA-4 antibodies in immunocompetent tumor models like B16-OVA and Pan02.