Adjudin (AF-2364) is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

which is under development as a potential non-hormonal

male contraceptive Male contraceptives, also known as male birth control, are methods of preventing pregnancy that solely involve the male physiology. The most common kinds of male contraception include condoms, outercourse, and vasectomy. In domestic animals, ca ...

drug, which acts by blocking the production of

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

in the

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...

, but without affecting

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

production. It is an analogue of the chemotherapy drug

lonidamine Lonidamine is a derivative of indazole-3-carboxylic acid, which for a long time, has been known to inhibit aerobic glycolysis in cancer cells. It seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This i ...

, an indazole-carboxylic acid, and further studies continue to be conducted into this family of drugs as possible contraceptives. , adjudin was in phase II human trials. As shown in mature male rats, the agent induces reversible

germ cell Germ or germs may refer to: Science * Germ (microorganism), an informal word for a pathogen * Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually * Germ layer, a primary layer of cells that forms during embry ...

loss from the seminiferous epithelium by disrupting cell adhesion function between Sertoli and germ cells. It weakens the adhesion between the

Sertoli cell Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimul ...

and maturing

leading to a sloughing and loss of the latter. As it does not affect spermatogonia themselves the loss of fertility is reversible. In experiments hormonal levels ( FSH, LH,

) were undisturbed during administration, and normal

spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...

returned in 95% of the tubules of rats at 210 days after the drug had been discontinued. When taken orally, the drug has very low

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

. The oral dose effective for contraception is so high that there have been side effects in the muscles and liver. Coupling an Adjudin molecule to a mutant form of

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...

may solve this problem. The mutant FSH is modified such that it no longer induces

Inhibin Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...

B production, but the membrane-bound FSH receptors on

Sertoli cells Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimula ...

still bind to it, delivering the Adjudin directly to the target cells. The adjudin-FSH can be either injected, delivered in an implant, or as a gel. A study in 2013 indicated that Adjudin, similar to its analogue

, has properties that inhibit cancer growth by targeting mitochondria and blocking energy metabolism in certain kinds of tumor cells in mice, indicating that it has potential as a drug for

cancer therapy Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ble ...

. It was invented by

Chuen Yan Cheng Chuen Yan Cheng () is a Senior Scientist for the Population Council's Center for Biomedical Research. He is most well known as the inventor of the non- steroid male contraceptive drug——Adjudin, which is the first male contraceptive drug on th ...

References

External links

"Trials for alternative male Pill show no side-effects"
at the Independent
"Sperm-stopping male pill hope"
at BBC News
Adjudin (a Lonidamine analogue)
at MaleContraceptives.org {{Hydrazines Contraception for males Experimental methods of birth control Indazoles Hydrazides Chloroarenes