GSK-2801

• CAT Number: I002077
• CAS Number: 1619994-68-1
• Molecular Formula: C₂₀H₂₁NO₄S
• Molecular Weight: 371.54
• Purity: ≥95%
• Target: Bromodomain
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 136 nM/257 nM(Kd, BAZ2A/BAZ2B)
• InChI: InChI=1S/C20H21NO4S/c1-4-11-25-15-9-10-21-18(14(2)22)13-17(19(21)12-15)16-7-5-6-8-20(16)26(3,23)24/h5-10,12-13H,4,11H2,1-3H3
• InChIKey: KHWCPNJRJCNVRI-UHFFFAOYSA-N
• SMILES: CC(C1=CC(C2=CC=CC=C2S(=O)(C)=O)=C3C=C(OCCC)C=CN13)=O

GSK2801 (CAT: I002077) is a potent and selective inhibitor of BAZ2A and BAZ2B bromodomains, which play a role in chromatin biology. It competitively binds to the acetyl-lysine binding site of BAZ2 bromodomains, with dissociation constants (KD) of 257 nM for BAZ2A and 136 nM for BAZ2B. Crystal structure analysis confirmed the acetyl-lysine competitive binding mode. In cellular studies, GSK2801 displaced GFP-BAZ2A from acetylated chromatin, demonstrating its cellular activity. Pharmacokinetic studies in mice revealed reasonable exposure after oral administration, with moderate clearance and plasma stability. GSK2801 serves as a valuable tool compound for investigating the function of BAZ2 bromodomains in chromatin biology through cellular and in vivo studies.

Reference

1: Yang X, Wu X, Zhang J, Zhang X, Xu C, Liao S, Tu X. Recognition of hyperacetylated N-terminus of H2AZ by TbBDF2 from Trypanosoma brucei. Biochem J. 2017 Nov 9;474(22):3817-3830. doi: 10.1042/BCJ20170619. PubMed PMID: 29025975.
2: Chen P, Chaikuad A, Bamborough P, Bantscheff M, Bountra C, Chung CW, Fedorov O, Grandi P, Jung D, Lesniak R, Lindon M, Müller S, Philpott M, Prinjha R, Rogers C, Selenski C, Tallant C, Werner T, Willson TM, Knapp S, Drewry DH. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. J Med Chem. 2016 Feb 25;59(4):1410-24. doi: 10.1021/acs.jmedchem.5b00209. Epub 2015 Apr 6. PubMed PMID: 25799074; PubMed Central PMCID: PMC4770311.