New approaches to male non-hormonal contraception

Nya-Ngatchou, Jean Jacques; Amory, John K.

doi:10.1016/j.contraception.2012.08.016

Cited by 36 publications

(29 citation statements)

References 31 publications

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“…Additionally, CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, and CDK2−/− knockout mice are viable but sterile 11–13 . Therefore, CDK2 also provides promise as a target for the development of non-hormonal male contraceptive agents that do not exhibit the significant side effects associated with hormone-based agents currently available for female contraception and under development for male contraception 14–16 .…”

Section: Introductionmentioning

confidence: 99%

Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases

et al. 2013

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Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009 – 0.0015 µM) from a single hit compound with weak inhibitory activity (IC50 = 15 µM), discovered by high-throughput screening. Structure-based design was performed using 35 co-crystal structures of CDK2 liganded with distinct analogues of the parent compound. The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4 and CDK6. Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 µM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics.

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Section: Introductionmentioning

confidence: 99%

Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases

et al. 2013

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“…54 Similarly, another derivative, H2-gamendazole, has been shown to induce 100% infertility after just one dose in male rats, and it is possible that this compound will progress to clinical trial. 55 However, it will need to show that it does not have long-term effects on the testis and that its contraceptive effect is reversible.…”

Section: Lonidamine Derivatives: Adjudin and Gamendazolementioning

confidence: 99%

“…57 RA binds RA receptors that control gene expression. 55 Certain compounds, such as bisdichloroacetyldiamines (eg, WIN 18446) have been shown to reversibly inhibit spermatogenesis by inhibiting testicular RA synthesis. 58 However, to be a viable contraceptive, they also must not interfere with retinoic function or synthesis in non-testicular tissue.…”

Section: Retinoic Acid (Ra)mentioning

confidence: 99%

An update on the potential for male contraception: emerging options

Garside¹,

Gebril²,

Alsaadi³

et al. 2013

OAJC

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The human population continues to grow and is estimated to rise to 10.1 billion by the end of the century. Therefore, there is still an unmet need for safe and highly effective contraceptive options for both men and women. Current options available to men include withdrawal, condoms, and vasectomy. Methods in development fall into two categories: hormonal and nonhormonal. This review will provide an overview of the testosterone combinations and immunocontraception of hormonal targets. Nonhormonal immunocontraception of sperm proteins will also be examined, together with the use of agents to disrupt other sperm-associated targets and pathways. The categories focused on include epididymal proteins, testicular kinases, epigenetic reader proteins, opioids, lonidamine derivatives, retinoic acid, microRNAs associated with spermatogenesis, and plant extracts. Considering these developments, the number of options available to men is likely to increase in the near future.

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“…Unfortunately this is a worldwide problem and, even in the USA, the statistics show a high rate of unintended pregnancies that end in abortion [191]. A correlation between unintended pregnancy, inadequate use and/or defective contraception choices has been proposed [193]. Thus, access to better and more effective contraception choices should result in improvement of newborn and maternal health [194].…”

Section: Future Perspectivesmentioning

confidence: 99%

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

Alves¹,

Dias²,

Silva³

et al. 2015

CMP

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Abstract:The development of a "male pill" to control fertility is still a major challenge. Although women have several options to play an active role in the couple family planning, men are very limited in terms of contraceptive methods. Several approaches have been proposed to develop a male contraceptive and can be divided in two major groups: hormonal and non-hormonal methods. Within the testis, the somatic Sertoli cell (SC) is known as the "nurse cell" since it provides the physical and nutritional support for the developing germ cells. Moreover, adjacent SCs form the Sertoli/blood testis barrier (BTB), which divides the seminiferous epithelium into the basal and the apical compartments, controlling the passage of substances to the site where germ cells develop. Among the several functions of SC, its metabolism and the production of lactate, acetate and other metabolic factors are essential for the normal occurrence of spermatogenesis. In the last years, several works have highlighted that the metabolic cooperation established between SCs and developing germ cells is compromised in several diseases associated with male subfertility/infertility. Notably, several metabolismassociated proteins are specifically expressed in the testis. Thus, there are several evidences illustrating that the control of male fertility can be achieved by targeting testicular cells metabolism. Herein, we discuss the metabolic cooperation in testis as a potential pharmacological target to counteract subfertility/infertility promoted by several diseases, particularly metabolic diseases. We also discuss how it can contribute to the development of a male contraceptive.

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New approaches to male non-hormonal contraception

Cited by 36 publications

References 31 publications

Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases

Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases

An update on the potential for male contraception: emerging options

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

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