Track topics on Twitter Track topics that are important to you
SMARCA2 (SWI/SNF Related Matrix Associated Actin Dependent Regulator Of Chromatin Subfamily A Member 2), also known as BRM (Brahma homolog) is a Snf2-family DNA-dependent ATPase. BRM, and its close homolog Brahma related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPase members of the large ATP-dependent SWI/SNF chromatin remodeling complexes involved in transcriptional regulation of gene expression. No small molecules modulating SWI/SNF chromatin remodeling activity via inhibition of its ATPase activity have been reported, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show anti-proliferative activity in a BRG1-mutant lung tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1 loss-of-function settings, and should enable probing the role of SWI/SNF function more broadly in different cancer contexts and other diseases.
This article was published in the following journal.
Name: Journal of medicinal chemistry
DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PAR...
β-Tryptase is released from mast cells upon degranulation in response to allergic and inflammatory stimuli. Human tryptase is a homotetrameric serine protease with 4 identical active sites directed t...
Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor that Accelerates Healing.
Diabetic foot ulcers (DFUs) are a significant health problem. A single existing FDA-approved drug for this ailment, becaplermin, is not standard-of-care. We previously demonstrated that upregulation o...
With the aim to identify novel influenza PB2 inhibitors with high potency and excellent pharmacokinetic parameters, we have designed and synthesized two new series of pyrimidine-fused heterocycle deri...
A new series of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as dual inhibitors of sodium glucose co-transporter proteins (SGLTs) were disclosed. Two methods were de...
Matrix metalloproteinases (MMPs) are a group of 24 zinc containing enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predo...
As potential biomarkers of pressure-related aortic damage, matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm because of the important role they pl...
The aim of this study is to evaluate the effects of different matricing techniques either sectional matrix or circumferential matrix on reproduction of optimum proximal contacts and contou...
This is a voluntary study to allow subjects who received placebo while on GEN-003-002 to be randomized, in a blinded manner, to 1 of 6 active combinations of GEN-003 and Matrix-M2. Object...
The purpose of this prospective clinical trial is to document the performance and clinical outcomes of Biomet Discovery Elbow.
One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.
Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.
MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.
A MutS homolog protein and component of post-replicative DNA MISMATCH REPAIR. It forms a heterodimer with MUTS HOMOLOG 2 PROTEIN (MSH2) and recognizes large insertion-deletion loops up to 13 nucleotides in length. This directs downstream events such as strand discrimination, excision, and resynthesis.
Orally active semisynthetic cephalosporin antibiotic with broad-spectrum activity.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...