Adjudin
   HOME

TheInfoList



OR:

Adjudin (AF-2364) is a drug 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 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 testoste ...
, 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 tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
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 emb ...
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-stimu ...
and maturing sperm 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,
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 tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
) were undisturbed during administration, and normal spermatogenesis 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%. Ho ...
. 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 may solve this problem. The mutant FSH is modified such that it no longer induces Inhibin 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
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 ...
, 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 bl ...
. It was invented by Chuen Yan Cheng.


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