New home for bromodomains

Lauren Martz
2012 Science-Business eXchange  
Researchers at the Dana-Farber Cancer Institute and the Baylor College of Medicine have shown that Tensha Therapeutics Inc.'s bromodomain inhibitors could prevent sperm production and be developed as a male contraceptive. 1 The biotech, which is focused on developing the molecules for cancer, has exclusive rights to the findings and is interested in pursuing bromodomain inhibitors in the indication. Available options for male contraception are limited to barrier methods and vasectomy. There are
more » ... no male contraceptive drugs on the market. Several hormone-based strategies are in the clinic but carry the risk of systemic side effects. Indeed, Michael O'Rand, professor of cell biology and developmental biology at The University of North Carolina at Chapel Hill, said not all men react the same way to testosterone-based contraceptives and that testosterone can cause increased aggression. Nor can the therapies be delivered orally because they are quickly destroyed in the body. These issues suggest nonhormonal strategies could be more successful. The first clues that bromodomain inhibitors could be good candidates emerged in 2007 when a group at Columbia University Medical Center found that genetic knockout of bromodomain testisspecific (BRDT), a bromodomain-containing protein specifically found in the testis, caused sterility in male mice. 2 Bromodomains are protein domains that bind to acetylated lysines and are involved in chromatin remodeling. Additional evidence that BRDT could be a male contraceptive target came in 2010 when a group at The University of Utah School of Medicine showed that mutations in BRDT were associated with male infertility in a genomewide association study. 3 Now, groups from Dana-Farber and Baylor have teamed up to determine how bromodomain inhibitors affect male fertility. The researchers found JQ1, a bromodomain inhibitor that acts against proteins including BRDT and bromodomain containing 4 (BRD4), had a hormone-independent contraceptive effect in male mice. The groups were led by James Bradner, assistant professor in the
doi:10.1038/scibx.2012.914 fatcat:67oz35covbdppebwfziy3edrgy