| Identification | Back Directory | [Name]
GSK620 | [CAS]
2088410-46-0 | [Synonyms]
GSK620
1-benzyl-N5-cyclopropyl-N3-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarboxamide | [Molecular Formula]
C18H19N3O3 | [MDL Number]
MFCD32899274 | [MOL File]
2088410-46-0.mol | [Molecular Weight]
325.36 |
| Chemical Properties | Back Directory | [Boiling point ]
618.6±55.0 °C(Predicted) | [density ]
1.30±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 62.5 mg/mL (192.09 mM; Need ultrasonic) | [form ]
Solid | [pka]
12.43±0.20(Predicted) | [color ]
White to off-white | [InChI]
InChI=1S/C18H19N3O3/c1-19-17(23)15-9-13(16(22)20-14-7-8-14)11-21(18(15)24)10-12-5-3-2-4-6-12/h2-6,9,11,14H,7-8,10H2,1H3,(H,19,23)(H,20,22) | [InChIKey]
QZZCUOVXHPAQRQ-UHFFFAOYSA-N | [SMILES]
C1(=O)N(CC2=CC=CC=C2)C=C(C(NC2CC2)=O)C=C1C(NC)=O |
| Hazard Information | Back Directory | [Uses]
GSK620 is a potent and orally active pan-BD2 inhibitor with excellent broad selectivity, developability and in vivo oral pharmacokinetics. GSK620 is highly selective for the BET-BD2 family of proteins, with >200-fold selectivity over all other bromodomains. GSK620 shows an anti-inflammatory phenotype in human whole blood[1]. | [Biological Activity]
GSK620 is a potent and orally active pan-BD2 inhibitor with excellent broad selectivity, developability and in vivo oral pharmacokinetics. GSK620 is highly selective for the BET-BD2 family of proteins, with >200-fold selectivity over all other bromodomains. GSK620 shows an anti-inflammatory phenotype in human whole blood[1].
GSK620 shows an anti-inflammatory phenotype in human whole blood. Human blood samples are stimulated with LPS, which produces a strong immune response. The monocyte chemattractant protein 1 (MCP-1/CCL2) is measured. This is a chemokine which recruits monocytes, memory T cells, and dendritic cells to sites of inflammation. GSK620 reduces the MCP-1 response in a concentration-dependent manner with (an expected) ～1 log drop off in potency relative to the biochemical BRD4 BD2 potencies observed[1].
Highlighting the utility of GSK620 as an in vivo tool, efficacy is observed in separate models of inflammatory arthritis, psoriasis, and hepatitis[1]. | [in vitro]
GSK620 shows an anti-inflammatory phenotype in human whole blood. Human blood samples are stimulated with LPS, which produces a strong immune response. The monocyte chemattractant protein 1 (MCP-1/CCL2) is measured. This is a chemokine which recruits monocytes, memory T cells, and dendritic cells to sites of inflammation. GSK620 reduces the MCP-1 response in a concentration-dependent manner with (an expected) ～1 log drop off in potency relative to the biochemical BRD4 BD2 potencies observed.
| [in vivo]
Highlighting the utility of GSK620 as an in vivo tool, efficacy is observed in separate models of inflammatory arthritis, psoriasis, and hepatitis.
| [References]
[1]. Seal JT, et al. The Optimization of a Novel, Weak Bromo and Extra Terminal Domain (BET) Bromodomain Fragment Ligand to a Potent and Selective Second Bromodomain (BD2) Inhibitor. J Med Chem. 2020;63(17):9093-9126. |
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