molecules of the month

sAC as a target for male contraception. Soluble adenylyl cyclase (sAC) is one of several ACs that catalyze the cyclization of ATP to form cyclic adenosine monophosphate (cAMP). cAMP is the second messenger in several signaling pathways including that which activates sperm to be capable of fertilizing eggs (“capacitation”). The target is genetically validated in humans, as two adult human males were recently diagnosed with infertility due to a sAC mutation that rendered their sperm immotile. sAC inhibitors such as TDI-11861 could be effective as on-demand, non-hormonal male contraceptives, a longstanding unmet medical need. Drug target residence time as a key property requirement. sAC is regulated by changes in cellular bicarbonate levels. Sperm are stored under low bicarbonate conditions (<5…