Adjudin Explained

Adjudin (AF-2364) is a drug which is under development as a potential non-hormonal male contraceptive drug, which acts by blocking the production of sperm in the testes, but without affecting testosterone production.[1] It is an analogue of the chemotherapy drug lonidamine, an indazole-carboxylic acid, and further studies continue to be conducted into this family of drugs as possible contraceptives.[2]

, adjudin was in phase II human trials.[3]

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.[4] [5] It weakens the adhesion between the Sertoli cell and maturing sperm leading to a sloughing and loss of the latter.[6] 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.[7]

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.[8] The mutant FSH is modified such that it no 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. The adjudin-FSH can be either injected, delivered in an implant, or as a gel.[9]

A study in 2013 indicated that Adjudin, similar to its analogue lonidamine, 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.[10]

It was invented by Chuen Yan Cheng.[11] [12] [13] [14]

External links

Notes and References

  1. Mruk DD . New perspectives in non-hormonal male contraception . Trends in Endocrinology and Metabolism . 19 . 2 . 57–64 . March 2008 . 18291665 . 10.1016/j.tem.2007.11.002 . 29435757 .
  2. Tash JS, Attardi B, Hild SA, Chakrasali R, Jakkaraj SR, Georg GI . A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose . Biology of Reproduction . 78 . 6 . 1127–38 . June 2008 . 18218612 . 10.1095/biolreprod.106.057810 . free .
  3. Male Contraceptive Methods Are in the Pipeline . Robert . Finn . vanc . Ob.gyn. News. 2007 . 10.1016/S0029-7437(07)70395-6 . 0029-7437. 42 . 9 . 28 . 31 January 2024 .
  4. Mruk DD, Cheng CY . Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis . Endocrine Reviews . 25 . 5 . 747–806 . October 2004 . 15466940 . 10.1210/er.2003-0022 . free .
  5. Lee NP, Wong EW, Mruk DD, Cheng CY . Testicular cell junction: a novel target for male contraception . Current Medicinal Chemistry . 16 . 7 . 906–15 . 2009 . 19275601 . 2804911 . 10.2174/092986709787549262 .
  6. Cheng CY, Mruk D, Silvestrini B, Bonanomi M, Wong CH, Siu MK, Lee NP, Lui WY, Mo MY . 6 . AF-2364 [1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide] is a potential male contraceptive: a review of recent data . Contraception . 72 . 4 . 251–61 . October 2005 . 16181968 . 10.1016/j.contraception.2005.03.008 .
  7. Grima J, Silvestrini B, Cheng CY . Reversible inhibition of spermatogenesis in rats using a new male contraceptive, 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide . Biology of Reproduction . 64 . 5 . 1500–8 . May 2001 . 11319158 . 10.1095/biolreprod64.5.1500 . free .
  8. Mruk DD, Wong CH, Silvestrini B, Cheng CY . A male contraceptive targeting germ cell adhesion . Nature Medicine . 12 . 11 . 1323–8 . November 2006 . 17072312 . 10.1038/nm1420 . 19460327 .
  9. Web site: Methods. Adjudin . 29 September 2010 . 11 October 2010 . https://web.archive.org/web/20101011035444/http://malecontraceptives.org/methods/adjudin.php . dead .
  10. Xie QR, Liu Y, Shao J, Yang J, Liu T, Zhang T, Wang B, Mruk DD, Silvestrini B, Cheng CY, Xia W . 6 . Male contraceptive Adjudin is a potential anti-cancer drug . Biochemical Pharmacology . 85 . 3 . 345–55 . February 2013 . 23178657 . 4108200 . 10.1016/j.bcp.2012.11.008 .
  11. Web site: Obsessed Scientist Finally Throttles 'Em! Non-Paternity Potion . The New York Observer. 2008-09-28. https://web.archive.org/web/20080924221042/http://www.observer.com/node/36309. dead. 2008-09-24.
  12. Web site: Future male "pill" targets testicles. 2008-09-28.
  13. Web site: Male pill - Science Base. 2008-09-28.
  14. Web site: Seed: The Hunt for Male Birth Control. 2008-09-28. https://web.archive.org/web/20081002153134/http://www.seedmagazine.com/news/2006/10/the_hunt_for_male_birth_contro.php. 2008-10-02. unfit.

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