Adjudin

Adjudin

Adjudin (AF-2364), also 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide, is an analogue of lonidamine, an indazole-carboxylic acid.

According to a May 1, 2007 news article by science writer Robert Finn in the twice-monthly newspaper Ob.Gyn.News about a presentation Future Contraception: What's in the Pipeline? by nurse-practitioner and nurse-midwife Sharon Schnare on March 8, 2007 at the Contemporary Forums Contraceptive Technology conference in San Francisco, "Adjudin is currently in phase II human trials".

As shown in mature male rats, the agent induces reversible germ cell loss from the seminiferous epithelium by disrupting cell adhesion function between Sertoli and germ cells. It weakens the adhesion between the Sertoli cell 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) 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. 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 not longer induces Inhibin B production, but the membrane-bound FSH receptors on Sertoli cells still bind to it, delivering the Adjudin directly to the target cells.

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