GCN5/PCAF Inhibitor

Butyrolactone 3 (MB-3) is a specifical small-molecule inhibitor of the histone acetyltransferase Gcn5 (IC₅₀=100 μM), which has a high affinity to the Gcn5 enzyme comparable to that of its natural substrate, histone H3. Butyrolactone 3 shows weak inhibitory on CBP (IC₅₀=0.5 mM). Butyrolactone 3 can be used in studies of cancer, metabolic, autoimmune and neurological diseases.

Anacardic Acid, extracted from cashew nut shell liquid, is a histone acetyltransferase inhibitor, inhibits HAT activity of p300 and PCAF, with IC₅₀s of ∼8.5 μM and ∼5 μM, respectively.

Garcinol, a polyisoprenylated benzophenone harvested from Garcinia indica, exerts anti-cholinesterase properties towards acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) with IC₅₀s of 0.66 μM and 7.39 μM, respectively. Garcinol also inhibits histone acetyltransferases (HATs, IC₅₀= 7 μM) and p300/CPB-associated factor (PCAF, IC₅₀ = 5 μM). Garcinol has anti-inflammatory and anti-cancer activity.

Prifetrastat (PF-07248144), a first-in-class, selective, and orally active KAT6A and KAT6AB inhibitor. Prifetrastat can be used for the study of ER+/HER2− breast cancer.

CPTH2 is a potent histone acetyltransferase (HAT) inhibitor. CPTH2 selectively inhibits the acetylation of histone H3 by Gcn5. CPTH2 induces apoptosis and decreases the invasiveness of a clear cell renal carcinoma (ccRCC) cell line through the inhibition of acetyltransferase p300 (KAT3B).

PU139 is a potent pan-histone acetyltransferase (HAT) inhibitor. PU139 blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) and p300 with IC₅₀s of 8.39, 9.74, 2.49 and 5.35 μM, respectively.

GSK 4027 is a chemical probe for the PCAF/GCN5 bromodomain with an pIC₅₀ of 7.4±0.11 for PCAF in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay.

AUR1545 is a selective KAT2A/KAT2B ((GCN5/PCAF)) PROTAC degrader that induces monocyte differentiation and inhibits the growth of acute myeloid leukemia cells. AUR1545 inhibits cell growth, induces epithelial differentiation and suppresses tumor growth in small cell lung cancer models. AUR1545 inhibits cell growth and induces differentiation in neuroendocrine prostate cancer cells and primary patient-derived organoids. AUR1545 is applicable to research related to acute myeloid leukemia, small cell lung cancer and neuroendocrine prostate cancer.

PCAF-IN-2 (compound 17) is a potent PCAF inhibitor with an IC₅₀ value of 5.31 µM. PCAF-IN-2 shows anti-tumour activity. CAF-IN-2 induces apoptosis and arrest the cell cycle at the G2/M phase.

NSC 694623 is a potent histone acetyltransferase (HAT) inhibitor with an IC₅₀ value of 15.9 μM for recombinant HAT p300/CBP-associated factor (PCAF). NSC 694623 has antiproliferative activity against certain cancer cells. NSC 694623 can be used for researching anticancer.

CBP/p300-IN-19 hydrochloride is a potent and selective p300/CBP HAT inhibitor with IC₅₀s of 1.4, 2.2, >100, >100 µM for p300-HAT, CBP-HAT, PCAF, Myst3, respectively. CBP/p300-IN-19 hydrochloride shows antitumor activity.

CAY10669 (compound 6d) is an anacardic acid (HY-N2020) derivative that inhibits histone acetyltransferase PCAF with an IC₅₀ of 662 μM. CAY10669 enhances the SAHA-induced acetylation in HEPG2 cells, exhibits cytotoxicity in zebrafish embryo, promotes transgene expression in CHO-K1 cells.

CPTH2 hydrochloride is a potent histone acetyltransferase (HAT) inhibitor. CPTH2 hydrochloride selectively inhibits the acetylation of histone H3 by Gcn5. CPTH2 hydrochloride induces apoptosis and decreases the invasiveness of a clear cell renal carcinoma (ccRCC) cell line through the inhibition of acetyltransferase p300 (KAT3B).

CCT077791 is a PCAF (IC₅₀: 7.3 μM (FlashPlate); 2.2 μM (Filter assay)) and p300 histone acetyltransferase inhibitor. CCT077791 reduces total acetylation of histones H3 and H4, levels of specific acetylated lysine marks, and acetylation of α-tubulin. CCT077791 can be used in the research of colorectal cancer.

CBP/p300-IN-19 is a potent p300/CBP HAT inhibitor with IC₅₀s of 1.4, 2.2, >100, >100 µM for p300-HAT, CBP-HAT, PCAF, Myst3, respectively. CBP/p300-IN-19 shows antitumor activity.