SAN DIEGO, March 13, 2016 --Women can choose from a wide selection of birth control methods, including numerous oral contraceptives, but there's never been an analogous pill for men. That's not for lack of trying: For many years, scientists have attempted to formulate a male pill. Finally, a group of researchers has taken a step toward that goal by tweaking some experimental compounds that show promise. 
 
 The researchers present their work today at the 251st National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 12,500 presentations on a wide range of science topics. 
 
 One compound that's been studied as a potential male contraceptive is testosterone. "At certain doses it causes infertility," says Jillian Kyzer, a graduate student working on the topic. "But at those doses, it doesn't work for up to 20 percent of men, and it can cause side effects, including weight gain and a decrease in 'good' cholesterol." 
 
 Bringing any male contraceptive to market requires it to satisfy several requirements, explains Kyzer's team leader, Gunda I. Georg, Ph.D., who is based at the University of Minnesota College of Pharmacy. It would have to be soluble so it could be taken by mouth. It would start working fairly quickly, and it wouldn't diminish libido. It would be safe even if taken for decades. And because some users would eventually want to have children, its impact on fertility would be reversible, with no lingering ill effects on sperm or embryos. "That's a very high bar for bringing a male contraceptive to market," Georg points out. 
 
 These hurdles have driven many investigators from the hunt, yet Georg's team perseveres. "It would be wonderful to provide couples with a safe alternative because some women cannot take birth control pills," she says. 
 
 Drug companies, including Bristol-Myers Squibb (BMS), have created some experimental male contraceptives, but these too have drawbacks, Kyzer says. For instance, one of the company's test compounds is good at inhibiting fertility but isn't very soluble, so it can't be taken by mouth. "No one wants to inject themselves with a needle once a day or once a week for most of their lives," she notes. 
 
 Another Bristol-Myers Squibb experimental compound can be taken orally but isn't very selective in terms of its cellular targets in the body. That means the compound not only interacts with the retinoic acid receptor-α, which is involved in male fertility, but also with two other retinoic acid receptors that are unrelated to fertility. That flaw could cause side effects. 
 
 Kyzer and several of her colleagues are creating numerous substances that are similar in their chemical structure to the Bristol-Myers Squibb compounds. Although the optimal contraceptive for men remains elusive, Georg's team has made some progress. For example, the researchers are gaining a better understanding of how tweaks to the chemical structure of their test compounds affect the substances' cellular interactions in the body. One of those tweaks added a polar group to the molecule, which made the test compounds more soluble. Another tweak replaced an amide bond in the BMS compound with slightly different bonds that are known in the field of medicinal chemistry to mimic an amide bond. As intended, that change improved the test compounds' stability, meaning they would last longer in the body. Unfortunately, both types of modifications also reduced the specificity of the compounds for the intended retinoic acid receptor-α target. 
 
 The group continues to refine the chemical structures to achieve the ultimate balance of solubility, specificity and stability as they aim to design a better male pill. They are now investigating hybrid compounds that incorporate scaffolds and structural features from several other compounds known to interact with the retinoic acid receptor. 
 
 ### 
 
 A press conference on this topic will be held Monday, March 14, at 10:30 a.m. Pacific time in the San Diego Convention Center. Reporters may check-in at Room 16B (Mezzanine) in person, or watch live on YouTube http://bit. ly/ ACSliveSanDiego . To ask questions online, sign in with a Google account. 
 
 The researchers acknowledge funding from the Contraception Research Branch, Eunice Kennedy Shriver National Institute of Child Health & Human Development. 
 
 The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 158,000 members, ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio. 
 
 To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org. 
 
 Note to journalists: Please report that this research is being presented at a meeting of the American Chemical Society. 
 
 Follow us: Twitter | Facebook 
 
 Title 
 
 Design and Synthesis of Nuclear Receptor Antagonists Targeting RARα for Male Contraception 
 
 Abstract 
 
 The retinoic acid receptor-α (RARα) is a nuclear receptor that has been implicated in male contraception. In the absence of retinoic acid, RARα has been shown to prevent spermatogenesis by inhibiting DNA transcription.1 Previous work by Bristol Myers Squibb identified two RAR antagonists of interest: BMS 189453 and BMS 189532. While BMS 189453 has been shown to cause reversible infertility in mice when administered orally, it is non-selective over the β and γ isoforms; BMS 189532 is selective for RARα, but lacks oral bioavailability. The goal of this project is to design and synthesize selective, bioavailable antagonists of RARα based on the BMS scaffold, which can be broken down into three regions: a hydrophobic ring, a linker, and a carboxylic acid. The antagonists are tested using an iterative design process. 
 
 The first generation of compounds developed in our lab contained varying aryl substituents on the ring region and amide bioisosteres in the linker region. The compounds were evaluated using protein crystallography, isothermal titration calorimetry, and a luciferase reporter assay. Analysis of the RARα co-crystal structures determined that additional lipophilic substituents on the ring portion of the scaffold could increase selectivity. Alternative ring structures, including chromenes, are being pursued. Synthesis and evaluation of these compounds will be discussed. 
 
 Reference 
 
 1. Chung, S. S. W.; Cuellar, R. A. D.; Wang, X.; Reczek, P. R.; Georg, G. I.; Wolgemuth, D. J. ACS Med. Chem. Lett. 2013, 4, 446-450. 

 We spoke to the researcher who has been trying to develop the ever-elusive solution to contraception for men for 10 years. 
 
 While women have been both ingesting and implanting various contraceptive methods for years, the promise of male birth control in any form is still annoyingly futuristic. Currently, the only male contraceptives that are anywhere near being close to market involve semi-invasive procedures. There's RISUG (Reversible Inhibition of Sperm Under Guidance)—a polymer contraceptive that's injected into the vas deferens to block sperm, but has only been available to men in India through clinical trials— and Vasalgel. There's also the Bimek SLV, or the "sperm switch." Invented by a German carpenter, the somewhat quirky device can mechanically control sperm through an on/off switch that has to be implanted behind the testicles. The project is currently seeking investors, but most men—including our boyfriends—aren't willing to go to such great lengths; surveys show that men, if given the choice, would rather take a daily pill. 
 
 Thankfully for those who aren't too keen on the idea of robotized balls, researchers at the University of Minnesota recently unveiled a promising breakthrough at the 251st National Meeting & Exposition of the American Chemical Society (ACS) in San Diego. Led by Dr. Gunda Georg, the team of researchers has been able to isolate a test compound that could build the scaffolding for a male birth control pill. 
 
 Read more: The Men Who Fake Orgasms 
 
 "The research on hormonal methods of male birth control involving testosterone has been going on for decades, but nothing has come to market," Georg tells Broadly over the phone. "We're now focusing on non-hormonal approaches." 
 
 Because testosterone "doesn't work for up to 20 percent of men, and it can cause side effects, including weight gain and a decrease in 'good' cholesterol," the researchers started exploring other options, according to a press release from Jillian Kyzer, a graduate student working on the project. Specifically, they're looking at how retinoic acid receptors regulate fertility. 
 
 "There are three receptors: alpha, beta, gamma," Georg explains. "Studies have been done in animals that have a deficiency in the alpha receptor. These animals are quite healthy and quite normal; they don't really need that receptor for anything other than sperm production. So if you could block that receptor [in humans], pharmacologically, you could induce infertility. Of course, once you stop the treatment, fertility would return normally." 
 
 Photo by Shikhar Bhattarai via Stocksy 
 
 
 
 Georg points out that with this method there would potentially be no side effects. "The animal studies were very promising in this regard," she says. 
 
 So far, Georg and her team of researchers have started working with an experimental compound from the pharmaceutical company Bristol-Myers Squibb that modifies the alpha receptor in men, though there have been some challenges. "We want to make sure it's only binding to the alpha receptor and not other receptors," which could cause unwanted side effects, Georg says. Another problem is that the compound is not currently very soluble, which means that there's still work that needs to be done before men have a pill that can be ingested orally. 
 
 Georg, however, is optimistic that the compound could be ready to test in animals in as little as six months. "Everything indicates that we're on the right track with this new approach," she says. 

 There are a lot of contraceptive methods available to women, and the oral contraceptive is just one of them. For men, however, there are only three known methods used today – vasectomy, condom and the pull-out method. There has never been an oral pill for men, but scientists claim they are a step closer to formulating the world's first male contraceptive pill. 
 
 For years, scientists have been trying to find the correct formula for a male contraceptive pill. Researchers from the University of Minnesota College of Pharmacy have been tweaking the chemicals used from previous attempts in the hopes of finding the successful combinations. 
 
 Researchers speculate that the form of contraception will cause temporary infertility among men without any short or long-term side effects. This will help a lot of women who are not allowed to take oral contraceptive pills specially those with high blood pressure, heart problems and are breastfeeding. 
 
 Lead researcher Dr. Gunda Georg points out that the prospect pill is safe even if taken for a long time. Its effect is also reversible in case the couple wanted to have children. 
 
 "That's a very high bar for bringing a male contraceptive to market," she says, speaking at the 251st National Meeting & Exposition of the American Chemical Society (ACS). 
 
 One of the key ingredients studied as a potential male contraceptive is testosterone, which at certain doses could cause infertility among men. 
 
 "At those doses, it doesn't work for up to 20 percent of men, and it can cause side effects, including weight gain and a decrease in 'good' cholesterol," says Jillian Kyzer, a graduate student who is part of the study. 
 
 Tweaking Structure Of Chemicals 
 
 Some pharmaceutical companies have explored the possibility of producing the world's first male contraceptive pill. They have reached experimental stages but some errors and flaws have persisted, according to Dr. Georg. 
 
 One attempt by Bristol-Myers Squibb (BMS) involved a test compound that was effective in making men infertile but was not soluble, which makes users unable to take it orally. Though it was deemed effective and promising, it was considered inconvenient. 
 
 "No one wants to inject themselves with a needle once a day or once a week for most of their lives," said Kyzer. 
 
 The company's second attempt involved a soluble compound but the molecule was unable to selectively target the cells required for inducing temporary infertility. It interacts with retinoic acid receptor-α (RAR-α, a protein involved in male fertility and two other retinoic acid receptors not involved in male fertility. This means that the compound may cause severe side effects. 
 
 Exploring Alternatives 
 
 The team is tinkering with the compounds used by BMS in their two previous attempts. The goal of the team is to make a compound that is both soluble and can target specific receptors in the body without causing adverse effects. They created several substances that are similar in chemical structure to the BMS compounds. 
 
 Though the male contraceptive pill is not yet produced, the team has made some progress. At present, the team continues to refine the recipe to achieve the desired solubility, specificity and stability. 
 
 Photo : Iain Watson | Flickr 
 
 © 2018 Tech Times, All rights reserved. Do not reproduce without permission.
– Right now, men really only have three choices when it comes to birth control: condoms, a vasectomy, or pulling out, Tech Times reports. But after decades of false starts, a male version of the pill is one step closer to hitting pharmacies, according to Broadly. "It would be wonderful to provide couples with a safe alternative because some women cannot take birth control pills," Dr. Gunda Georg says in an American Chemical Society press release. Georg and her team at the University of Minnesota are working with "an experimental compound" that would ideally be taken orally to stop sperm with no negative effects on health or libido and no lasting impact on fertility. But, as Georg says, that's a "very high bar." The compound researchers are working with blocks one of three retinoic acid receptors—the alpha receptor—related to fertility. Studies show animals with a deficiency in that receptor are healthy except for sperm production. "If you could block that receptor, pharmacologically, you could induce infertility," Georg tells Broadly. So far, researchers are having a hard time tweaking the compound to make sure it hits only the alpha receptor (thus avoiding side effects) while also being able to be taken orally. "No one wants to inject themselves with a needle once a day or once a week," researcher Jillian Kyzer says in the press release. But the team believes it's close to getting it right, with Georg predicting they'll have a pill ready for animal tests in half a year. (But will the CDC tell men who don't go on birth control not to drink, like they did women?)