This probe is available to purchase from Tocris, Cayman Chemical and Sigma.
The control may be requested by clicking here.
For any inquiries please contact firstname.lastname@example.org.
Abbvie has developed a potent acetyl-CoA competitive histone acetyltransferase (HAT) inhibitor of p300/CBP and has donated A-485 and its control A-486 to the SGC probe collection, following review of published data along SGC probe guidelines.
A-485 is a potent and selective HAT inhibitor of p300/CBP in vitro with an IC50 of 10 nM in a p300 TR-FRET assay and 3 nM in a CBP TR-FRET assay with selectivity > 1000-fold over closely related HATs. SPR data indicates potent binding to p300 (KD=15 nM). In PC-3 cells A-485 reduces H3K27ac with IC50 of 73 nM while not affecting H3K9ac levels. Inhibition of cellular proliferation is observed in several cancer cell types, most notably AR+ prostate, multiple myeloma, and NHL. A-486 is a suitable control with 1000-fold higher IC50 in the p300 TR-FRET assay.
A-486 (Negative Control)
Physical and chemical properties for A-485
No. of chiral centres
No. of rotatable bonds
No. of hydrogen bond acceptors
No. of hydrogen bond donors
Physical and chemical properties for A-486 (Negative Control)
Analysis of high content microscopy shows that A-485 (but not A-486) decreases H3K27Ac (open squares), but not H3K9Ac (closed squares) levels after three hours of treatment in PC-3 cells. Error bars represent the s.d. of n = 3 independent biological replicates
A-485 selectively inhibits production of p300 acetylation products H3K27Ac and H3K18Ac after three hours of treatment in PC-3 cells (n = 2).
1. Overall structure of Δp300 HAT domain with A-485
2. Overlay of Lys-CoA structure indicating A-485 binds in CoA site
3. Shape of A-485 binding pocket
4. Key interactions of the binding of A-485 to Δp300 HAT domain