JQ1

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JQ1
JQ1 structure.png
Systematic (IUPAC) name
(S)-tert-butyl 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate
Clinical data
Legal status ?
Identifiers
CAS number 1268524-70-4 YesY
ATC code ?
PubChem CID 46907787
ChemSpider 26323622
Chemical data
Formula C23H25ClN4O2S 
Mol. mass 456.987

JQ1 is a chemical compound which is under development as a non-hormonal male contraceptive drug. Its chemical structure is a triazolothienodiazepine, a series originally discovered by Mitsubishi Pharma [WO/2009/084693], related to benzodiazepine derivatives such as etizolam, however JQ1 does not produce sedative or anxiolytic effects and is instead a potent and selective inhibitor of the bromodomain testis-specific protein BRDT,[1] which is essential for chromatin remodeling during spermatogenesis. By blocking BRDT, JQ1 effectively blocks the production of sperm in the testes and consequently produces effective contraception, without the negative side effects associated with previously researched hormonal contraceptives for men.[2] JQ1 has also been investigated for other applications in the treatment of HIV infection,[3] heart disease,[4] and some forms of cancer.[5][6]

See also[edit]

References[edit]

  1. ^ Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W. B.; Fedorov, O.; Morse, E. M.; Keates, T.; Hickman, T. T.; Felletar, I.; Philpott, M.; Munro, S.; McKeown, M. R.; Wang, Y.; Christie, A. L.; West, N.; Cameron, M. J.; Schwartz, B.; Heightman, T. D.; La Thangue, N.; French, C. A.; Wiest, O.; Kung, A. L.; Knapp, S.; Bradner, J. E. (2010). "Selective inhibition of BET bromodomains". Nature 468 (7327): 1067–1073. doi:10.1038/nature09504. PMC 3010259. PMID 20871596.  edit
  2. ^ Matzuk, M. M.; McKeown, M. R.; Filippakopoulos, P.; Li, Q.; Ma, L.; Agno, J. E.; Lemieux, M. E.; Picaud, S.; Yu, R. N.; Qi, J.; Knapp, S.; Bradner, J. E. (2012). "Small-Molecule Inhibition of BRDT for Male Contraception". Cell 150 (4): 673–684. doi:10.1016/j.cell.2012.06.045. PMC 3420011. PMID 22901802.  edit
  3. ^ Banerjee, C.; Archin, N.; Michaels, D.; Belkina, A. C.; Denis, G. V.; Bradner, J.; Sebastiani, P.; Margolis, D. M.; Montano, M. (2012). "BET bromodomain inhibition as a novel strategy for reactivation of HIV-1". Journal of Leukocyte Biology 92 (6): 1147–1154. doi:10.1189/jlb.0312165. PMC 3501896. PMID 22802445.  edit
  4. ^ Anand Priti, et al "BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure" (2013) http://www.cell.com/abstract/S0092-8674%2813%2900884-2
  5. ^ Zuber, J.; Shi, J.; Wang, E.; Rappaport, A. R.; Herrmann, H.; Sison, E. A.; Magoon, D.; Qi, J.; Blatt, K.; Wunderlich, M.; Taylor, M. J.; Johns, C.; Chicas, A.; Mulloy, J. C.; Kogan, S. C.; Brown, P.; Valent, P.; Bradner, J. E.; Lowe, S. W.; Vakoc, C. R. (2011). "RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia". Nature 478 (7370): 524–528. doi:10.1038/nature10334. PMC 3328300. PMID 21814200.  edit
  6. ^ Ott, C. J.; Kopp, N.; Bird, L.; Paranal, R. M.; Qi, J.; Bowman, T.; Rodig, S. J.; Kung, A. L.; Bradner, J. E.; Weinstock, D. M. (2012). "BET bromodomain inhibition targets both c-MYC and IL7R in high-risk acute lymphoblastic leukemia". Blood 120 (14): 2843–2852. doi:10.1182/blood-2012-02-413021. PMC 3466965. PMID 22904298.  edit