1300031-49-5

Basic information

• Product Name: I-BET151 (GSK1210151A)
• Synonyms: 7-(3,5-Dimethyl-4-isoxazolyl)-1,3-dihydro-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-2H-imidazo[4,5-c]quinolin-2-one;GSK 1210151A;I-BET 151;I-BET 151/GSK 1210151A;GSK1210151A (I-BET151);7-(3,5-diMethylisoxazol-4-yl)-8-Methoxy-1-((R)-1-(pyridin-2-yl)ethyl)-1H-iMidazo[4,5-c]quinolin-2(3H)-one;7-(3,5-Dimethylisoxazol-4-yl)-8-methoxy-1-((R)-1-(pyridin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-2;7-(3,5-Dimethyl-4-isoxazolyl)-1,3-dihydro-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-2H-imidazo[4,5-c]quinolin-2-one I-BET151(GSK1210151A)
• CAS NO: 1300031-49-5
• Molecular Formula: C23H21N5O3
• Molecular Weight: 415.44454
• Product Categories: Inhibitors
• Mol File: 1300031-49-5.mol
• Article Data: 5

Chemical Properties

• Appearance: white to beige/
• Density: 1.314
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble20mg/mL, clear
• PKA: 11.14±0.20(Predicted)
• CAS DataBase Reference: I-BET151 (GSK1210151A)(CAS DataBase Reference)
• NIST Chemistry Reference: I-BET151 (GSK1210151A)(1300031-49-5)
• EPA Substance Registry System: I-BET151 (GSK1210151A)(1300031-49-5)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 1300031-49-5(Hazardous Substances Data)

Usage

Description

I-BET151 (GSK1210151A) is an isoxazole class pan-BET family inhibitor that selectively blocks the bromodomain and extra terminal (BET) proteins BRD2, BRD3, and BRD4. These proteins play a key role in various cellular processes, including inflammatory gene expression, mitosis, and viral/host interaction by controlling the assembly of histone acetylation-dependent chromatin complexes. I-BET151 is an off-white solid with potential anti-inflammatory and anti-cancer properties.

Uses

Used in Pharmaceutical Industry:
I-BET151 (GSK1210151A) is used as a bromodomain inhibitor for treating mixed-lineage leukemia (MLL)-fusion leukemia. It blocks the BET proteins, leading to the suppression of leukemic cell growth and inducing apoptosis or G0/G1 cell cycle arrest in MLL-fusion cell lines.
Used in Anti-inflammatory Applications:
I-BET151 (GSK1210151A) is used as an anti-inflammatory agent for its potential to upregulate ApoA1 expression within the nanomolar range in human hepatic cell line HepG2, suggesting its potential anti-inflammatory activities upon administration.
Used in Research and Development:
I-BET151 (GSK1210151A) is used as a research tool to study the inhibitory effect of BET recruitment to chromatin, providing insights into the role of BET proteins in various cellular processes and their potential as therapeutic targets for different diseases.

Biological activity

I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.

In vitro

I-BET151 exhibits potent selectivity over an extensive range of diverse protein types such as COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, ion channels, and transporters. Similar to I-BET762 (GSK525762A), I-BET151 displays potent binding affinity to BRD2, BRD3 and BRD4 with KD of 0.02-0.1 μM, and significantly inhibits lipopolysaccharide-stimulated IL-6 cytokine production in human peripheral blood mononuclear cells (PBMC) and whole blood (WB) as well as rat WB with IC50 of 0.16 μM, 1.26 μM, and 1.26 μM, respectively. I-BET151 (0.5 or 5 μM) inhibits the binding of BETs (BRD2, BRD3, BRD4, and BRD9) but not the binding of 23 other bromodomain proteins in HL60 nuclear extract to acetylated histone peptides. I-BET151 has potent efficacy against cell lines harboring different MLL-fusions such as MV4;11, RS4;11, MOLM13, and NOMO1 cells with IC50 of 15-192 nM. Consistently, I-BET151 completely ablates the colony-forming potential of MLL-fusion-driven leukaemias (MOLM13) but not leukaemias driven by tyrosine kinase activation (K562). I-BET151 also displays potent efficacy in both liquid culture and clonogenic assays using primary murine progenitors transformed with either MLL-ENL or MLL-AF9. I-BET151 treatment significantly induces apoptosis and prominent G0/G1 arrest in MLL-fusion cell lines driven by distinct MLL fusions (MOLM13 and MV4;11 containing MLL-AF9 and MLL-AF4, respectively) but not the K562 cells, probably due to the inhibition of transcription of BCL2, C-MYC and CDK6 by blocking the recruitment of BRD3/4, PAFc and SEC components into transcriptional start site (TSS).

In vivo

Administration of I-BET151 at 30 mg/kg/day significantly inhibits tumor growth of murine MLL-AF9 and human MLL-AF4 leukaemia in mice, and provides marked survival benefit.

References

http://www.selleckchem.com/products/i-bet151-gsk1210151a.html

Biochem/physiol Actions

GSK1210151A (I-BET151) is an inhibitor of the BET (bromodomain and extra terminal domain protein) family of acetyl-lysine recognizing, chromatin ′adaptor′ proteins. GSK1210151A displaces BRD3 and BRD4, PAFc and SEC components from chromatin resulting in inhibition of transcription at key genes (BCL2, C-MYC and CDK6) involved in the initiation of mixed lineage leukemia (MLL). GSK1210151A (I-BET151) showed good efficacy in 2 MLL animal models.

Upstream product

• 16114-47-9 3,5-dimethylisoxazole-4-boronic acid 
• 5399-03-1 2-iodo-1-methoxy-4-nitrobenzene 
• 1300031-62-2 3,5-dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole 
• 1300031-61-1 [3-(3,5-dimethyl-4-isoxazolyl)-4-(methyloxy)phenyl]amine 
• 1300735-40-3 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[1-(2-pyridinyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one 
• 1300737-83-0 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[1-(2-pyridinyl)ethyl]amino}-3-quinolinecarboxamide 
• 1300031-60-0 1,3-diethyl 2-([[3-(3,5-dimethyl-1,2-oxazol-4-yl)-4-methoxyphenyl]amino]methylidene)propanedioate 
• 1300031-59-7 ethyl 7-(3,5-dimethyl-4-isoxazolyl)-4-hydroxy-6-(methyloxy)-3-quinolinecarboxylate 
• 1300031-58-6 7-(3,5-dimethyl-4-isoxazolyl)-4-hydroxy-6-(methyloxy)-3-quinolinecarboxylic acid 
• 1300031-57-5 4-chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-3-quinolinecarboxamide 
• 1300737-69-2 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-(2-pyridinyl)ethyl]amino}-3-quinolinecarboxamide 
• 1300031-59-7 C₁₈H₁₈N₂O₅ 
• 1300031-58-6 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid 
• 27854-90-6 (R)-1-(pyridin-2-yl)ethanamine 

Relevant articles and documents

METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE

The present disclosure relates to compounds and methods for modulating the expression of dmpk, and treating diseases and conditions in which dmpk plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.

From ApoA1 upregulation to BET family bromodomain inhibition: Discovery of I-BET151

The discovery, synthesis and biological evaluation of a novel series of 7-isoxazoloquinolines is described. Several analogs are shown to increase ApoA1 expression within the nanomolar range in the human hepatic cell line HepG2.

IMIDAZO [4, 5-C] QUINOLINE DERIVATES AS BROMODOMAIN INHIBITORS

Novel compounds of Formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.