1355554-13-0Relevant academic research and scientific papers
Design, synthesis, and biological activity evaluation of a series of novel sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia
Chen, Aiping,Feng, Ziying,Huang, Wenlong,Li, Jieming,Liu, Xinhong,Qian, Hai,Qiu, Qianqian,Shi, Jing,Shi, Wei,Zhang, Wenjie,Zhou, Daoguang
, (2021)
Accumulating researches have contributed much effect to discover novel chemotherapeutic drug for leukemia with expeditious curative effect, of which bromodomain-containing protein 4 (BRD4) inhibitor is considered as a eutherapeutic drug which has presented efficient cell proliferation suppression effect. In this study, we disclosed a series of phenylisoxazole sulfonamide derivatives as potent BRD4 inhibitors. Especially, compound 58 exhibited robust inhibitory potency toward BRD4-BD1 and BRD4-BD2 with IC50 values of 70 and 140 nM, respectively. In addition, compound 58 significantly suppressed cell proliferation of leukemia cell lines HL-60 and MV4-11 with IC50 values of 1.21 and 0.15 μM. In-depth study of the biological mechanism of compound 58 exerted its tumor suppression effect via down-regulating the level of oncogene c-myc. Moreover, in vivo pharmacokinetics (PK) study was conducted and the results demonstrated better pharmacokinetics features versus (+)-JQ1. In summary, our study discovers that compound 58 represents as a novel BRD4 inhibitor for further investigation in development of leukemia inhibitor with potentiality.
BRD4 protein inhibitor with anti-tumor activity and preparation method and application thereof
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, (2019/07/04)
The invention discloses a compound as shown in a formula (I) with anti-tumor activity or pharmaceutically acceptable ester or salt and a preparation method thereof and the application thereof as a BRD4 protein inhibitor. Compared with the prior art, the B
Fragment-based discovery of bromodomain inhibitors part 2: Optimization of phenylisoxazole sulfonamides
Bamborough, Paul,Diallo, Hawa,Goodacre, Jonathan D.,Gordon, Laurie,Lewis, Antonia,Seal, Jonathan T.,Wilson, David M.,Woodrow, Michael D.,Chung, Chun-Wa
, p. 587 - 596 (2012/03/26)
Bromodomains are epigenetic reader modules that regulate gene transcription through their recognition of acetyl-lysine modified histone tails. Inhibitors of this protein-protein interaction have the potential to modulate multiple diseases as demonstrated by the profound anti-inflammatory and antiproliferative effects of a recently disclosed class of BET compounds. While these compounds were discovered using phenotypic assays, here we present a highly efficient alternative approach to find new chemical templates, exploiting the abundant structural knowledge that exists for this target class. A phenyl dimethyl isoxazole chemotype resulting from a focused fragment screen has been rapidly optimized through structure-based design, leading to a sulfonamide series showing anti-inflammatory activity in cellular assays. This proof-of-principle experiment demonstrates the tractability of the BET family and bromodomain target class to fragment-based hit discovery and structure-based lead optimization.
