1395084-25-9

Basic information

• Product Name: MS436
• Synonyms: 4-[(1E)-2-(2-Amino-4-hydroxy-5-methylphenyl)diazenyl]-N-2-pyridinylbenzenesulfonamide;4-[(1E)-2-(2-Amino-4-hydroxy-5-methylphenyl)diazenyl]-N-2-pyridinylbenzenesulfonamide MS436;MS436 4-[(1E)-2-(2-Amino-4-hydroxy-5-methylphenyl)diazenyl]-N-2-pyridinylbenzenesulfonamide;MS 436, >=98%;MS436
• CAS NO: 1395084-25-9
• Molecular Formula: C₁₈H₁₇N₅O₃S
• Molecular Weight: 383.42428
• Product Categories: Inhibitors
• Mol File: 1395084-25-9.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 673.7±65.0 °C(Predicted)
• Appearance: /
• Density: 1.42±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; insoluble in EtOH; ≥19.15 mg/mL in DMSO
• PKA: 9.25±0.36(Predicted)
• CAS DataBase Reference: MS436(CAS DataBase Reference)
• NIST Chemistry Reference: MS436(1395084-25-9)
• EPA Substance Registry System: MS436(1395084-25-9)

Safety Data

• Hazardous Substances Data: 1395084-25-9(Hazardous Substances Data)

Usage

Description

MS436, through a set of water-mediated interactions, exhibits low nanomolar affinity (estimated Ki of 30-50 nM) with preference for the first bromodomain over the second. MS436 effectively blocks BRD4 transcriptional activity in lipopolysaccharide-induced production of both nitric oxide and IL-6 in mouse macrophages (IC50 values are 3.8 and 4.9 ?M, respectively). MS436 represents a new class of bromodomain inhibitors and will facilitate further investigation of the biological functions of the two bromodomains of BRD4 in gene expression.

Uses

MS 436 is a potent bromodomain inhibitor, binding to BRD4 and more tightly to subdomain BD1 than BD2. These domains play a key role in inflammatory gene expression, mitosis and viral/host interaction. Applications involving innhibition of bromodomains include decrease in cell proliferation for leukemia and destruction of tumor cells.

Biological Activity

ms436 is a potent and selective small-molecule inhibitor of brd4 with ki values of ＜0.085μm and 0.34μm, respectively for brd1 and brd2 [1].brd4 plays a role in gene transcription and is a drug target for cancer and inflammation. it has two bromodomains. ms436 is a diazobenzene compound, it is designed from the sar studies to have higher selectivity. in vitro fluorescent anisotropy assay shows ms436 has about 10-fold higher affinity of brd1 over brd2. ms436 binds to brd4 through a set of water-mediated interaction and this is the molecular basis for the binding affinity. ms436 also has activity to cbp brd. in raw264.7 cells, ms436 can block nf-κb-directed no production and block the expression of proinflammatory cytokine interleukin (il)-6 induced by lps [1].

references

[1] zhang g, plotnikov an, rusinova e, shen t, morohashi k, joshua j, zeng l, mujtaba s, ohlmeyer m, zhou mm. structure-guided design of potent diazobenzene inhibitors for the bet bromodomains. j med chem. 2013 nov 27;56(22):9251-64.

Upstream product

• 1028-11-1 4-nitro-N-(pyridin-2-yl)benzenesulfonamide 
• 504-29-0 2-aminopyridine 
• 98-74-8 4-Nitrobenzenesulfonyl chloride 
• 19077-98-6 N-acetylsulfapyridine 
• 144-83-2 sulphapyridine 
• 2835-95-2 amino-4 hydroxy-2 toluene 

Relevant articles and documents

Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains

BRD4, characterized by two acetyl-lysine binding bromodomains and an extra-terminal (ET) domain, is a key chromatin organizer that directs gene activation in chromatin through transcription factor recruitment, enhancer assembly, and pause release of the RNA polymerase II complex for transcription elongation. BRD4 has been recently validated as a new epigenetic drug target for cancer and inflammation. Our current knowledge of the functional differences of the two bromodomains of BRD4, however, is limited and is hindered by the lack of selective inhibitors. Here, we report our structure-guided development of diazobenzene-based small-molecule inhibitors for the BRD4 bromodomains that have over 90% sequence identity at the acetyl-lysine binding site. Our lead compound, MS436, through a set of water-mediated interactions, exhibits low nanomolar affinity (estimated Ki of 30-50 nM), with preference for the first bromodomain over the second. We demonstrated that MS436 effectively inhibits BRD4 activity in NF-κB-directed production of nitric oxide and proinflammatory cytokine interleukin-6 in murine macrophages. MS436 represents a new class of bromodomain inhibitors and will facilitate further investigation of the biological functions of the two bromodomains of BRD4 in gene expression.