| Bioactivity | 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]. | ||||||||||||
| Invitro | 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]. | ||||||||||||
| In Vivo | Highlighting the utility of GSK620 as an in vivo tool, efficacy is observed in separate models of inflammatory arthritis, psoriasis, and hepatitis[1]. | ||||||||||||
| Name | GSK620 | ||||||||||||
| CAS | 2088410-46-0 | ||||||||||||
| Formula | C18H19N3O3 | ||||||||||||
| Molar Mass | 325.36 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |