GSK699 is a potent, cell-permeable proteolysis targeting chimera (PROTAC) that selectively degrades the histone acetyltransferases PCAF (KAT2B) and GCN5 (KAT2A). In biochemical assays, GSK699 exhibited high affinity for PCAF and GCN5 bromodomains with K<sub>d</sub> values in the low nanomolar range. In cellular models, treatment with 1 µM GSK699 for 4 hours resulted in near-complete degradation of both PCAF and GCN5 proteins in THP-1 and HEK293 cells, confirmed by Western blot analysis. Degradation was shown to be VHL-dependent, with a DC<sub>50</sub> (half-maximal degradation concentration) of ~200 nM in THP-1 cells. Functional assays demonstrated downstream suppression of PCAF/GCN5-regulated gene expression, indicating effective target engagement and transcriptional modulation. These data support GSK699 as a valuable chemical tool for probing the biological roles of PCAF/GCN5 and the therapeutic potential of their targeted degradation.
MedKoo Cat#: 408004
Name: GSK699
CAS#: 2260944-68-9
Chemical Formula: C45H51BrN8O7
Exact Mass: 894.3064
Molecular Weight: 895.86
Elemental Analysis: C, 60.33; H, 5.74; Br, 8.92; N, 12.51; O, 12.50
The following data is based on the product molecular weight 895.86 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Bassi ZI, Fillmore MC, Miah AH, Chapman TD, Maller C, Roberts EJ, Davis LC, Lewis DE, Galwey NW, Waddington KE, Parravicini V, Macmillan-Jones AL, Gongora C, Humphreys PG, Churcher I, Prinjha RK, Tough DF. Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach. ACS Chem Biol. 2018 Oct 19;13(10):2862-2867. doi: 10.1021/acschembio.8b00705. Epub 2018 Sep 18. PubMed PMID: 30200762.
