Sacyl Pharmaceuticals is pioneering an innovative concept: non-hormonal, reversible contraception via acute inhibition of soluble adenylyl cyclase (sAC; ADCY10) in sperm.
To fertilize the ovulated oocyte, sperm deposited in the vagina need to be motile to travel through cervix, uterus, and uterotubal junction, and they need to acquire the ‘capacity’ to fertilize (a.k.a., capacitation). Activation of sAC inside sperm is genetically and pharmacologically validated as required for both, sperm motility and capacitation. Inhibition of sAC thus prevents fertilization by blocking capacitation and sperm progression through the female reproductive tract.
Watch a short presentation on the scientific approach (7 min) here.
Normal movement of human sperm Inhibitor binds to sAC … … and blocks sperm motility.
Additional Information
Timeline - From sAC discovery to drug development
1999 – Soluble Adenylyl Cyclase (sAC, ADCY10) discovered
2005 - sAC is shown to be a bicarbonate sensor
2005 – sAC knockout mice generated, potential for male contraception (among other indications)
2005 – 2010 – Extensive advances in sAC biology, including assay development and structural biology
2014 – Mechanism of bicarbonate activation of sAC discovered
2016 – Selective sAC inhibitor LRE1 discovered
2018 - LevBuck lab and TDI initiated male contraceptive program
2019 – Infertile, but healthy, men with sAC frameshift mutation identified
2020 – Prototype sAC inhibitor tool compound TDI-10229 rendered mouse and human sperm immotile in vitro
2022 – Potent, long off rate sAC inhibitor TDI-11861 discovered
2022 – Sacyl Pharmaceuticals formed
2023 – On demand, sAC male contraceptive Proof of Concept achieved
2023 – Sacyl Pharma drug discovery efforts initiated
Key scientific papers
For additional information please visit our NEWS page, with resources from scientific publications and from media outlets.
Balbach M, Rossetti T, Ferreira J, Ghanem L, Ritagliati C, Myers RW, Huggins DJ, Steegborn C, Miranda IC, Meinke PT, Buck J, Levin LR (2023) On-demand male contraception via acute inhibition of soluble adenylyl cyclase. Nat Commun 14:637. doi: 10.1038/s41467-023-36119-6.
Miller M, Rossetti T, Ferreira J, Ghanem L, Balbach M, Kaur N, Levin LR, Buck J, Kehr M, Coquille S, van den Heuvel J, Steegborn C, Fushimi M, Finkin-Groner E, Myers RW, Kargman S, Liverton NJ, Huggins DJ, Meinke PT (2022) Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates. J Med Chem 65, 15208-15226.