Searching across hundreds of databases
First-generation bromodomain extra-terminal protein (BETP) inhibitors (BETi) (e.g., OTX015) that disrupt binding of BETP BRD4 to chromatin transcriptionally attenuate AML-relevant progrowth and prosurvival oncoproteins. BETi treatment induces apoptosis of AML BPCs, reduces in vivo AML burden and induces clinical remissions in a minority of AML patients. Clinical efficacy of more potent BETis, e.g., ABBV-075 (AbbVie, Inc.), is being evaluated. Venetoclax and A-1210477 bind and inhibit the antiapoptotic activity of BCL2 and MCL1, respectively, lowering the threshold for apoptosis. BETi treatment is shown here to perturb accessible chromatin and activity of enhancers/promoters, attenuating MYC, CDK6, MCL1 and BCL2, while inducing BIM, HEXIM1, CDKN1A expressions and apoptosis of AML cells. Treatment with venetoclax increased MCL1 protein levels, but cotreatment with ABBV-075 reduced MCL1 and Bcl-xL levels. ABBV-075 cotreatment synergistically induced apoptosis with venetoclax or A-1210477 in patient-derived, CD34+ AML cells. Compared to treatment with either agent alone, cotreatment with ABBV-075 and venetoclax was significantly more effective in reducing AML cell-burden and improving survival, without inducing toxicity, in AML-engrafted immune-depleted mice. These findings highlight the basis of superior activity and support interrogation of clinical efficacy and safety of cotreatment with BETi and BCL2 or MCL1 inhibitor in AML.
Pubmed ID: 30647404 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsA research-based biopharmaceutical company that develops advanced therapies to address global health problems.
View all literature mentionsCell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Bim (C34C5) Rabbit mAb
View all literature mentionsThis monoclonal targets Bcl-2 (100)
View all literature mentionsThis monoclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal targets Mcl-1
View all literature mentionsThis polyclonal targets Phospho-Histone H2A.X (Ser139)
View all literature mentionsThis polyclonal targets Cleaved PARP (Asp214) (Human Specific)
View all literature mentionsThis monoclonal targets p21 Waf1/Cip1
View all literature mentionsThis monoclonal targets Cdk6 (H-11)
View all literature mentionsThis polyclonal targets BRD4
View all literature mentionsThis monoclonal targets c-Myc (D84C12) XP Rabbit mAb
View all literature mentionsCell line SKM-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SET-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Image analysis software that acquires, analyzes, and archives research data without altering raw findings. It integrates data and changes how pixels are mapped to the screen for clearer display, rather than altering the pixels of the image data itself.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsCell line OCI-AML-5 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MOLM-13 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsAn Antibody supplier
View all literature mentionsThis monoclonal targets Bcl-2 (100)
View all literature mentionsCell line SKM-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Bim (C34C5) Rabbit mAb
View all literature mentionsCell line SET-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
