Nearly half of all pregnancies worldwide are unintended. The global contraceptive market size worth $25 Billion by 2030. My goal is to develop small-molecule contraceptives targeting sperm-egg fusion in fertilization. IZUMO1 is exclusively expressed in the testes. My lab has generated monoclonal antibodies against human IZUMO1 that completely inhibits fertilization. To date, there is no report of small-molecule IZUMO1 inhibitors. Compared to antibody-based approaches, small molecules offer distinct advantages: greater efficacy, improved safety profiles, and global accessibility. Moreover, the shorter half-lives of small molecules make their contraceptive effects both on-demand and reversible. My proposal outlines a new strategy to discovering small-molecule anti-IZUMO1 drugs.