Acetaminophen (paracetamol) is a selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 25.8 μM; is a widely used antipyretic and analgesic drug.
PU-139 is a potent, unselective HAT (Histone acetyltransferase) inhibitor that blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB protein (CBP) and p300; triggers caspase-independent cell death in cell culture, blocks growth of SK-N-SH neuroblastoma xenografts in mice, and synergizes the effect of doxorubicin in vivo.
I-CBP112 is a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor, that targets the CBP/p300 bromodomains.
PU-141 is a potent, selective CBP/p300 inhibitor that inhibits SK-N-SH cell growth with GI50 of 0.48 uM; blocks growth of SK-N-SH neuroblastoma xenografts in mice, also reduces histone lysine acetylation in vivo at concentrations that block neoplastic xenograft growth.
NSC 698600 is a potent PCAF inhibitor, with IC50 of 6.51 µM (PCAF/H31-21). NSC 698600 exhibits good activity of inhibiting the proliferation of cancer cells[1].
Ep300/CREBBP-IN-3 (Example 61) is a potent Ep300 and CREBBP inhibitor with IC50s of 0.056 and 0.095 μM, respectively. Ep300/CREBBP-IN-3 can be used for the research of cancer[1].
JG-2016 is a potent inhibitor of histone acetyltransferase 1 (HAT1), with an IC50 of 14.8 μM in the HAT1 acetylation assays[1].
CBP/p300-IN-21 (Compound 5d) is a selective CBP/p300 inhibitor (IC50: 0.07 and 1.755 μM for p300 and CBP). CBP/p300-IN-21 decreases H3K18Ac level. CBP/p300-IN-21 inhibits growth of 4T1 tumor growth in mice[1].
GNE-049 is a highly potent and selective CBP inhibitor with an IC50 of 1.1 nM in TR-FRET assay. GNE-049 also inhibits BRET and BRD4(1) with IC50s of 12 nM and 4200 nΜ, respectively.
CF53 is a highly potent, selective and orally active inhibitor of BET protein, with a Ki of <1 nM, Kd of 2.2 nM and an IC50 of 2 nM for BRD4 BD1. CF53 binds to both the BD1 and BD2 domains of BRD2, BRD3, BRD4, and BRDT BET proteins with high affinities, Kds are 1.1 nM (BRD2 BD1), 0.6 nM (BRD2 BD2), 0.52 nM (BRD3 BD1), 0.49 nM (BRD3 BD2), 0.8 nM (BRD4 BD2), 2 nM (BRDT BD1), 2.1 nM (BRDT BD2), 47 nM (CREBBP), 570 nM (CECR2), 110 nM (EP300), respectively, very selective over non-BET bromodomain-containing proteins. CF53 shows potent anti-tumor activity both in vitro and in vivo[1].
CBP/p300-IN-17 (compound 7) is a potent EP300/CBP HAT inhibitor with IC50s of 0.18, 0.69 µM for HAT EP300 and LK2 H3K27, respectively[1].
L002 is a novel potent, specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 uM. L002 has weak inhibitory effects against PCAF and GCN5 (IC50s =35 and 34 µM, respectively) and is specific for p300 over a panel of additional acetyltransferases, deacetylases, and methyltransferases[1]. L002 blocks histone acetylation and p53 acetylation, and inhibits STAT3 activation[2].
DS-9300 is a potent, orally active, selective EP300/CBP HAT inhibitor with an IC50 value of 28 nM. DS-9300 has anticancer activity and can be used in prostate cancer disease research[1].
Ep300/CREBBP-IN-2 (Example 73) is a potent and orally active Ep300 and CREBBP inhibitor with IC50s of 0.052 and 0.148 μM, respectively. Ep300/CREBBP-IN-2 can be used for the research of cancer[1].
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)[1][2].
MG149 is a selective and potent Tip60 inhibitor with IC50 of 74 uM, similar potentcy for MOF(IC50= 47 uM); little potent for PCAF and p300(IC50 >200 uM).IC50 value: 74/47 uM (Tip60/MOF) [1]Target: Tip60/MOFMG 149, at 200 μM, inhibited about 90% of Tip60 activity but had no inhibitory impact on p300 and PCAF. MG 149 was essentiallycompetitive with Ac-CoA and noncompetitive with the histone substrate. HAT inhibition studies with MG 149 demonstrated that both compounds inhibited the HAT activity of the nuclear extractsof different regions significantly (p < 0.05).
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[1]. 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[2].
Remodelin is a novel potent and selective inhibitor of the acetyl-transferase protein NAT10.IC50 value:Target: NAT10 inhibitorRemodelin can improve nuclear architecture, chromatin organization, and fitness of both human lamin A/C-depleted cells and HGPS-derived patient cells, and decrease markers of DNA damage in these cells. Using a combination of chemical, cellular, and genetic approaches, acetyl-transferase protein NAT10 was identified as the target of Remodelin that mediated nuclear shape rescue in laminopathic cells via microtubule reorganization. Down-regulation and mutations of the nuclear-architecture proteins lamin A and C cause misshapen nuclei and altered chromatin organization associated with cancer and laminopathies, including the premature-aging disease Hutchinson-Gilford progeria syndrome (HGPS). Remodelin is a useful chemical tool to study how NAT10 affects nuclear architecture and suggest alternative strategies for treating laminopathies and aging.
TPOP146 is a selective CBP/P300 benzoxazepine bromodomain inhibitor with Kd values of 134 nM and 5.02 μM for CBP and BRD4.
TH1834 dihydrochloride (TH-1834, TH 1834) is a novel potent specific histone acetyltransferase Tip60 inhibitor; induces apoptosis in breast cancer cell lines with more cytotoxicity than staurosporine; increases the γH2AX foci in the cancer cell lines PC-3 and DU-145 combined with IR; induces apoptosis and increases unrepaired DNA damage in breast cancer cells.
MOZ-IN-2 is an inhibitor of protein MOZ, a member of histone acetyltransferases, with an IC50 of 125 μM.
CTPB is a good activator of p300 histone acetyl transferase (HAT) enzyme[1].
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.
P300/CBP-IN-6 is a p300/CBP histone acetyltransferase (HAT) inhibitor extracted from patent WO2019161162A1, compound 33, has an IC50 of 330 nM for p300 HAT[1].
TH1834 (TH-1834, TH 1834) is a novel potent specific histone acetyltransferase Tip60 inhibitor; induces apoptosis in breast cancer cell lines with more cytotoxicity than staurosporine; increases the γH2AX foci in the cancer cell lines PC-3 and DU-145 combined with IR; induces apoptosis and increases unrepaired DNA damage in breast cancer cells.
Pocenbrodib (compound II) is a CBP/p300 family of bromodomain inhibitor. Pocenbrodib has the potential for cancer research[1].
Ep300/CREBBP-IN-8 (Example 37) is a potent and orally active Ep300 and CREBBP inhibitor with IC50s of 0.014 and 0.018 μM, respectively. Ep300/CREBBP-IN-8 can be used for the research of cancer[1].
Procyanidin B3 is a natural product, acts as a specific HAT inhibitor, binds to the other site of p300 instead of the active site, selectively inhibits p300-mediated androgen receptor acetylation. Procyanidin B3 has no effect on HDAC or HMT (histone methyltransferase)[1].
Histone Acetyltransferase Inhibitor II is a potent and cell permeable p300 inhibitor, with an IC50 of 5 µM; Histone Acetyltransferase Inhibitor II can be used in cancer research.
EML425 is a potent and selective CREB binding protein (CBP)/p300 inhibitor with IC50s of 2.9 and 1.1 μM, respectively.