7v2j › Citations

Design, synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl) sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia.

<div class='caption-title'>Chemical structures of representative BRD4 inhibitors.</div>
Scheme 1
<div class='caption-title'>Structure–based design of new benzo[d]isoxazole derivatives.</div>
Zhang MF, Luo XY, Zhang C, Wang C, Wu XS, Xiang QP, Xu Y, Zhang Y
OpenAccess logo Acta Pharmacol Sin 43 2735-2748 (2022)
Cited: 2 times
EuropePMC logo PMID: 35264812

Abstract

BRD4 plays a key role in the regulation of gene transcription and has been identified as an attractive target for cancer treatment. In this study, we designed 26 new compounds by modifying 3-ethyl-benzo[d]isoxazole core with sulfonamides. Most compounds exhibited potent BRD4 binding activities with ΔTm values exceeding 6 °C. Two crystal structures of 11h and 11r in complex with BRD4(1) were obtained to characterize the binding patterns. Compounds 11h and 11r were effective for BRD4(1) binding and showed remarkable anti-proliferative activity against MV4-11 cells with IC50 values of 0.78 and 0.87 μM. Furthermore, 11r (0.5-10 μM) concentration-dependently inhibited the expression levels of oncogenes including c-Myc and CDK6 in MV4-11 cells. Moreover, 11r (0.5-10 μM) concentration-dependently blocked cell cycle in MV4-11 cells at G0/G1 phase and induced cell apoptosis. Compound 11r may serve as a new lead compound for further drug development.

Articles - 7v2j mentioned but not cited (1)

  1. Design, synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl) sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia. Zhang MF, Luo XY, Zhang C, Wang C, Wu XS, Xiang QP, Xu Y, Zhang Y. Acta Pharmacol Sin 43 2735-2748 (2022)


Articles citing this publication (1)

  1. Crystal structure of [1,2,4]triazolo[4,3-b]pyridazine derivatives as BRD4 bromodomain inhibitors and structure-activity relationship study. Kim JH, Pandit N, Yoo M, Park TH, Choi JU, Park CH, Jung KY, Lee BI. Sci Rep 13 10805 (2023)


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