|S7110||(+)-JQ1||<1 mg/mL||91 mg/mL||91 mg/mL|
|S2780||I-BET151 (GSK1210151A)||<1 mg/mL||<1 mg/mL||27 mg/mL|
|S1216||PFI-1 (PF-06405761)||<1 mg/mL||69 mg/mL||<1 mg/mL|
|S7189||I-BET-762||<1 mg/mL||84 mg/mL||42 mg/mL|
|S7295||Apabetalone (RVX-208)||<1 mg/mL||74 mg/mL||<1 mg/mL|
|S7256||SGC-CBP30||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7233||Bromosporine||<1 mg/mL||81 mg/mL||<1 mg/mL|
|S7088||UNC1215||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7360||OTX015||<1 mg/mL||98 mg/mL||98 mg/mL|
|S7373||UNC669||<1 mg/mL||11 mg/mL||68 mg/mL|
|S8179||BI-7273||<1 mg/mL||70 mg/mL||70 mg/mL|
|S8190||CPI-637||<1 mg/mL||27 mg/mL||<1 mg/mL|
|S7853||CPI-0610||<1 mg/mL||73 mg/mL||12 mg/mL|
|S7304||CPI-203||<1 mg/mL||79 mg/mL||5 mg/mL|
|S7305||MS436||<1 mg/mL||55 mg/mL||1 mg/mL|
|S7906||PFI-4||<1 mg/mL||17 mg/mL||5 mg/mL|
|S7231||GSK2801||<1 mg/mL||74 mg/mL||7 mg/mL|
|S8589||SF2523||<1 mg/mL||29 mg/mL||7 mg/mL|
|S7315||PFI-3||<1 mg/mL||64 mg/mL||<1 mg/mL|
|S8400||Mivebresib(ABBV-075)||<1 mg/mL||91 mg/mL||<1 mg/mL|
|S8265||GSK6853||<1 mg/mL||81 mg/mL||81 mg/mL|
|S8496||EED226||<1 mg/mL||73 mg/mL||<1 mg/mL|
|S8180||PF-CBP1 HCl||100 mg/mL||100 mg/mL||100 mg/mL|
|S8344||AZD5153||<1 mg/mL||100 mg/mL||27 mg/mL|
|S7835||I-BRD9||<1 mg/mL||99 mg/mL||<1 mg/mL|
|S7620||GSK1324726A (I-BET726)||<1 mg/mL||86 mg/mL||86 mg/mL|
|S8113||BI-9564||<1 mg/mL||3 mg/mL||16 mg/mL|
|S7681||OF-1||<1 mg/mL||76 mg/mL||<1 mg/mL|
- Epigenetic Reader Domain阻害剤(28)
(+)-JQ1 is a BET bromodomain inhibitor, with IC50 of 77 nM/33 nM for BRD4(1/2) in cell-free assays, binding to all bromodomains of the BET family, but not to bromodomains outside the BET family.
The BET protein inhibitor JQ1 reduces c-Myc expression and attenuates primary MCC cell proliferation. A, decreased c-Myc expression in MCC-3 and MCC-5 treated with JQ1 (800 nmol/L) for 72 hours by qRT-PCR and immunoblotting. The mRNA expression of target genes was normalized to that of MRPS2 and a value of 1.0 was assigned to the mRNA expression of target genes in the control group (means+SEM; **, P < 0.01 vs. control); b-actin was used as a loading control for immunoblotting.
I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.
OVTOKO and OVCA420 cells were treated with DMSO, JQ1 (1 μM) or I-BET151 (1 μM). Cell lysates were immunoblotted with indicated antibodies.
PFI-1 is a highly selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC50 of 0.22 μM and for BRD2 with IC50 of 98 nM in a cell-free assay.
I-BET-762 is an inhibitor for BET proteins with IC50 of ~35 nM in a cell-free assay, suppresses the production of proinflammatory proteins by macrophages and blocks acute inflammation, highly selective over other bromodomain-containing proteins.
A., B. and C. Dose response curves of MPNST-derived cell lines treated with three bromodomain inhibitors: JQ1, OTX015 and I-BET-762.
Apabetalone (RVX-208) is a potent BET bromodomain inhibitor with IC50 of 0.510 μM for BD2 in a cell-free assay, about 170-fold selectivity over BD1. Phase 2.
Bromodomain 1 or 2 of BET family proteins is involved in 3T3-L1 adipogenesis. (A) LY294002, RVX208 and JQ1 were applied to differentiating 3T3-L1 from day 2 to day 6. Phenyl acetate (PA), known as a PPAR-γ agonist was used as a positive control. Cells were labeled with ORO (Bar=50nm). (B) Schematic representation of specificity of each chemical inhibitor for Bromodomain BD1 and 2 and quantitative analysis of ORO staining. The IDMR treatment without drugs (CTL) was used to define 100%. Data are reported as means ± sd (n=3); *** p<0.001 vs IDM control; ### p<0.001 vs IDMR control (-)-JQ1); +++ p<0.01 vs IDM of each condition; ns, non significant.
SGC-CBP30 is a potent CREBBP/EP300 inhibitor with IC50 of 21 nM and 38 nM in cell-free assays, respectively. Exhibits 40-fold and 250-fold selectivity for CBP over the first BRD of BRD4 (BRD4(1)) and BRD4(2) respectively.
Immuno-blot analysis of protein crotonylation after NaCr treatment in the absence or presence of p300/CBP inhibitors.
Bromosporine is a broad spectrum inhibitor for bromodomains with IC50 of 0.41 μM, 0.29 μM, 0.122 μM and 0.017 μM for BRD2, BRD4, BRD9 and CECR2, respectively.
UNC1215 is a potent and selective MBT (malignant brain tumor) antagonist, which binds L3MBTL3 with IC50 of 40 nM and Kd of 120 nM, 50-fold selective versus other members of the human MBT family.
OTX015 is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Phase 1.
A. Growth inhibition IC50 values of CUDC-907 and three BET inhibitors (I-BET-762, JQ1, and OTX015) in three BRD–NUT fusion-positive NMC cell lines. Cell viability after 72-hour incubation was assessed by the CellTiter-Glo assay. Growth inhibition IC50 values for each compound were determined by GraphPad Prism 5.
UNC669 is a potent and selective MBT (malignant brain tumor) inhibitor with IC50 of 6 μM for L3MBTL1, 5- and 11-fold selective over L3MBTL3 and L3MBTL4.
BI-7273 is a potent, selective, and cell-permeable BRD9 BD Inhibitor.
CPI-637 is a selective and cell-active benzodiazepinone CBP/EP300 bromodomain inhibitor.
CPI-0610 is a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor and currently undergoing human clinical trials for hematological malignancies.
CPI-203 is a potent BET bromodomain inhibitor with IC50 of 37 nM for BRD4.
MS436 is a selective BET bromodomain inhibitor with Ki of <0.085 μM and 0.34 μM for BRD4 (1) and BRD4 (2), respectively.
PFI-4 is a potent and selective BRPF1 bromodomain inhibitor with IC50 of 80 nM.
GSK2801 is a selective bromodomains BAZ2A/B inhibitor with KD of 257 nM and 136 nM, respectively.
SF2523 is a highly selective and potent inhibitor of PI3K with IC50 values of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.
PFI-3 is a selective chemical probe for SMARCA bromodomains, including SMARCA2, SMARCA4 and PB1(5) bromodomains.
Western blot analysis of Brg1, α-SMA and Col1a1 expression in the presence of PFI-3(0uM, 5uM, 10uM,20uM,40uM,80uM) for 48 h in the indicated concentration in LX-2 cells.
Mivebresib(ABBV-075) is a novel BET family bromodomain inhibitor. It binds bromodomains of BRD2/4/T with similar affinities (Ki of 1-2.2 nM) and highly selective for 18 bromodomain proteins tested (Kd > 1 μM; more than 600-fold selectivity vs. BRD4), but exhibits roughly 10-fold weaker potency towards BRD3 (Ki of 12.2 nM) and has moderate activity towards CREBBP (Kd = 87 μM; 54-fold selectivity vs. BRD4).
GSK6853 is a selective benzimidazolone BRPF1 inhibitor with pIC50 of 8.1(TR-FRET) showing greater than 1600-fold selectivity over all other bromodomains tested.
EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED.
PF-CBP1 HCl is a highly selective inhibitor of the bromodomain of CREB-binding protein(CREBBP).It inhibits CREBBP and p300 bromodomains with IC50 of 125 and 363 nM respectively.
AZD5153 is a potent, selective, and orally available BET/BRD4 bromodomain inhibitor with pKi of 8.3 for BRD4.
I-BRD9 (GSK602) is a potent and selective BRD9 inhibitor with pIC50 of 7.3, while it displayed a pIC50 of 5.3 against BRD4.
GSK1324726A (I-BET726) is a highly selective inhibitor of BET family proteins with IC50 of 41 nM, 31 nM, and 22 nM for BRD2, BRD3, and BRD4, respectively.
BI-9564 is a selective inhibitor of BRD9 and BRD7 bromodomains with the IC50 of 75 nM and 3.4 µM, respectively.
OF-1 is a potent inhibitor of BRPF1B and BRPF2 bromodomain with Kd of 100 nM and 500 nM, respectively.