1286631-83-1

Upstream product

• 40106-12-5 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide 
• 123-08-0 4-hydroxy-benzaldehyde 
• 502-42-1 cycloheptanone 
• 40106-13-6 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid ethyl ester 
• 767-00-0 4-cyanophenol 

Relevant academic research and scientific papers

Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That Induces AMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell Death in Breast Cancer

Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of the pharmacophore and WPF interaction optimization, we designed a small-molecule inhibitor of BRD4, 9f (FL-411) which was validated by cocrystal structure with BD1 of BRD4. Subsequently, 9f was discovered to induce ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction and thus activating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer cells. Interestingly, the iTRAQ-based proteomics analyses revealed that 9f induced ACD pathways involved in HMGB1, VDAC1/2, and eEF2. Moreover, 9f displayed a therapeutic potential on both breast cancer xenograft mouse and zebrafish models. Together, these results demonstrate that a novel small-molecule inhibitor of BRD4 induces BRD4-AMPK-modulated ACD in breast cancer, which may provide a candidate drug for future cancer therapy.

BRD4 inhibitors and applications thereof in tumor treating medicines

The invention relates to BRD4 targeting inhibitors and applications thereof in tumor treating medicines, and belongs to the technical field of antitumor pharmacy. A technical problem to be overcome is to provide compounds adopted as the BRD4 inhibitors. The compounds include compounds shown as follows, or pharmaceutically acceptable salts thereof. The compounds or the pharmaceutically acceptable salts thereof can be adopted as the BRD4 inhibitors and have obvious breast cancer treating effects.

Exploiting drug-resistant enzymes as tools to identify thienopyrimidinone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H

The thienopyrimidinone 5,6-dimethyl-2-(4-nitrophenyl)thieno[2,3-d] pyrimidin-4(3H)-one (DNTP) occupies the interface between the p66 ribonuclease H (RNase H) domain and p51 thumb of human immunodeficiency virus reverse transcriptase (HIV RT), thereby indu