6h-thieno[3-2-f][1-2-4]triazolo[4-3-a][1-4]diazepine-6-acetamide--4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2-3-9-trimethyl---(6s)- has been researched along with Neoplasms* in 3 studies
3 other study(ies) available for 6h-thieno[3-2-f][1-2-4]triazolo[4-3-a][1-4]diazepine-6-acetamide--4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2-3-9-trimethyl---(6s)- and Neoplasms
| Article | Year |
|---|---|
Discovery of selective HDAC/BRD4 dual inhibitors as epigenetic probes.
According to the binding mode of ABBV-744 with bromodomains and the cape space of HDAC, the novel selective HDAC/BRD4 dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. Evaluating the biomolecular activities through SARs exploration identified three kinds of selective dual inhibitors 41c (HDAC1/BRD4), 43a (pan-HDAC/BRD4) and 43d (HDAC6/BRD4(BD2)), whose target-related cellular activities in MV-4-11 cells were also confirmed. Significantly, the selective dual inhibitor 41c (HDAC1/BRD4) exhibited synergistic effects against MV-4-11 cells, which strongly induced G0/G1 cell cycle arrest and apoptosis, and the first HDAC6/BRD4(BD2) dual inhibitor was found. This study provides support for selective HDAC/BRD4 dual inhibitors as epigenetic probes based on pyrrolopyridone core for the future biological evaluation in different cancer cell lines. Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Drug Design; Drug Discovery; Drug Screening Assays, Antitumor; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Models, Molecular; Neoplasms; Pyridines; Pyridones; Pyrroles; Transcription Factors | 2021 |
Structure-Based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors.
BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound Topics: Animals; Antineoplastic Agents; Cell Cycle Proteins; Cell Proliferation; Crystallography, X-Ray; Drug Design; Drug Discovery; Humans; Inhibitory Concentration 50; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Nude; Mice, SCID; Microsomes, Liver; Molecular Structure; Neoplasm Transplantation; Neoplasms; Nuclear Proteins; Peptides; Protein Domains; Proteins; Transcription Factors | 2019 |
Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment.
Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3-a]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay. The substantial antiproliferative activities in human cancer cell lines, promising drug-like properties, and the selectivity for the BET family make the lead compound (13) as a novel BRD4 inhibitor motif for anti-cancer drug discovery. Topics: Animals; Antineoplastic Agents; Binding Sites; Cell Cycle Checkpoints; Cell Line, Tumor; Drug Evaluation, Preclinical; Half-Life; Humans; Inhibitory Concentration 50; Molecular Docking Simulation; Neoplasms; Nuclear Proteins; Protein Structure, Tertiary; Proto-Oncogene Proteins c-myc; Quinoxalines; Rats; Structure-Activity Relationship; Triazoles | 2017 |