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Frontiers in Medical Science Research, 2019, 1(1); doi: 10.25236/FMSR.20190106.

Research Advanced in Small Molecular Inhibitors of Human BRDT which for male contraceptives development


Juan Zhang, Hui Li

Corresponding Author:
Juan Zhang

Reproductive Medicine Center of Zhuzhou Central Hospital, Zhuzhou, China


Testis specific Bromodomain proteins (BRDT) belong to the BET protein (Bromodomain and extra-terminal),which only expressed in testis . Recent studies have found that broad-spectrum BET protein inhibitor JQ1 can affect the binding between the BD1 domain of BRDT and acetylated histone H4, thus inhibiting sperm formation. Therefore, it has become a star molecule in male reproductive mechanism research and contraceptive drug development. At present, several research on BRDT inhibitors has started by using JQ1-based virtual screening and  in vitro binding assay to screen out a variety of small molecular compounds that can effectively reduce the activity of BRDT. In this paper, the progress in this field in recent years is reviewed, and the screening direction of this kind of small molecule compounds in the later stage is analyzed and discussed.


Testicular specific bromine domain protein; Male antifertility; Spermatogenesis; Virtual screening

Cite This Paper

Juan Zhang, Hui Li, Research Advanced in Small Molecular Inhibitors of Human BRDT which for male contraceptives development. Frontiers in Medical Science Research (2019) Vol. 1 Issue 1: 61-67. https://doi.org/10.25236/FMSR.20190106.


[1] Chen SR, Batool A, Wang YQ, et al.(2016). The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon's head to tail. Cell Death Dis, vol. 7, no.11, pp. e2472.
[2] Bryant JM, Berger SL(2012). Low-hanging fruit: targeting Brdt in the testes. EMBO J, vol.31, no.19, pp.3788-9.
[3] Wolgemuth DJ, Griswold MD, Grimes DA(2012). Parsing the potential of a new male contraceptive. Nat Med, vol.18, no.10, pp.1466-7.
[4] Lambert JP, Picaud S, Fujisawa T, et al. (2019). Interactome rewiring following pharmacological targeting of BET Bromodomains. Mol Cell vol.73, no. 3, pp.621-38.
[5] Shi J, Vakoc CR(2014). The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell, vol.54, no.5, pp.728-36.
[6] Smith SG,Zhou MM(2016). The Bromodomain: a new target in emerging epigenetic medicine. ACS Chem Biol, vol.11(3, pp.598-608.
[7] Manterola M, Brown TM, Oh MY, Garyn C, et al(2018). BRDT is an essential epigenetic regulator for proper chromatin organization, silencing of sex chromosomes and crossover formation in male meiosis. PLoS Genet, vol.14, no.3, pp.e1007209.
[8] Morinière J, Rousseaux S, Steuerwald U, et al(2009). Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature, vol.461, no.7264, pp.664-8. 
[9] Matzuk MM, McKeown MR, Filippakopoulos P, et al. (2012). Small-molecule inhibition of BRDT for male contraception. Cell, vol.150, no.4, pp.673-84.
[10] Gao N, Ren J, Hou L, et al. (2016). Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening. Int J Mol Med, vol.38, no.1, pp.39-44.
[11] Ayoub AM, Hawk LML, Herzig RJ, et al. (2017). BET Bromodomain Inhibitors with One-Step Synthesis Discovered from Virtual Screen.J Med Chem, vol.60, no.12, pp.4805-17.
[12] Tanaka M, Roberts JM, Seo HS, et al. (2016). Design and characterization of bivalent BET inhibitors. Nat Chem Biol, vol.;12, no.12, pp.1089-96.