Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia was written by Picaud, Sarah;Leonards, Katharina;Lambert, Jean-Philippe;Dovey, Oliver;Wells, Christopher;Fedorov, Oleg;Monteiro, Octovia;Fujisawa, Takao;Wang, Chen-Yi;Lingard, Hannah;Tallant, Cynthia;Nikbin, Nikzad;Guetzoyan, Lucie;Ingham, Richard;Ley, Steven V.;Brennan, Paul;Muller, Susanne;Samsonova, Anastasia;Gingras, Anne-Claude;Schwaller, Juerg;Vassiliou, George;Knapp, Stefan;Filippakopoulos, Panagis. And the article was included in Science Advances in 2016.Recommanded Product: 1619994-69-2 This article mentions the following:
Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clin. studies and have motivated drug development efforts targeting non-BET BRDs. However, the complexmultidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacol. targeting. To address this issue, we developed a promiscuous BRD inhibitor [bromosporine (BSP)] that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle, we studied the effects of BSP on leukemic cell lines known to be sensitive to BET inhibition and found, as expected, strong antiproliferative activity. Comparison of the modulation of transcriptional profiles by BSP after a short exposure to the inhibitor resulted in a BET inhibitor signature but no significant addnl. changes in transcription that could account for inhibition of other BRDs. Thus, nonselective targeting of BRDs identified BETs, but not other BRDs, as master regulators of contextdependent primary transcription response. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Recommanded Product: 1619994-69-2).
Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine and derivatives coordinate readily with transition metals to form complexes and catalysts with synthetic utility.Recommanded Product: 1619994-69-2
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem