| Name | GNE-781 |
| Description | GNE-781 is a highly potent and selective inhibitor of CBP (IC50: 0.94 nM in TR-FRET assay). GNE-781 also inhibits BRET and BRD4(1) (IC50s: 6.2 nM and 5100 nM, respectively). |
| In vitro | GNE-781 decreases FOXP3 (forkhead box P3) transcript levels. GNE-781 is a highly advanced potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element-binding protein, binding protein. GNE-781 is exquisitely selective for CBP/P300 and is remarkably selective for CBP (5425-fold) and P300 (4250-fold), which is shown by an examination of a subset of bromodomains. GNE-781 displays an appropriate balance of cell potency, selectivity (5425-fold over BRD4(1)) [1]. |
| In vivo | GNE-781 is a highly potent and selective inhibitor of CBP that is efficacious in a MOLM-16 AML xenograft model. GNE-781 shows antitumor activity in an AML tumor model and is also shown to reduce Foxp3 transcript levels in a dose-dependent manner and it also shows moderate to low clearance in vivo in all species evaluated, with acceptable oral bioavailability. The effect of GNE-781 is determined in an in vivo PK/PD experiment using a MOLM-16 (adult AML cell line) xenograft mouse model. GNE-781(3 and 30 mg/kg; Single doses) are given in MOLM-16 tumor-bearing animals, and samples are collected at time points covering 2-24 h. Upon tumor establishment, Administration with GNE-781(3-30 mg/kg; twice daily ). Single-agent efficacy is observed at all doses, as evidenced by inhibition of MOLM-16 tumor growth. Tumor growth inhibition (%TGI) is 73%, 71%, and 89% at 3, 10, and 30 mg/kg, respectively. All doses of GNE-781 are well tolerated over the 21-day dosing window, with a maximal body weight loss of 3.7%. Tumor RNA is generated and used to assess MYC transcript by quantitative RT-PCR relative to vehicle-treated animals. At doses as low as 3 mg/kg at 2 and 8 h, suppression of MYC is observed, with maximal suppression observed at 10 and 30 mg/kg at 2 h (87% and 88% inhibition, respectively). To evaluate the in vivo efficacy of GNE-781, MOLM-16 AML xenografts are established in SCID beige mice[1]. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 95 mg/mL (180.75 mM), Sonication is recommended.
Ethanol : 95 mg/mL (180.75 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (3.81 mM), Sonication is recommended.
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| Keywords | Inhibitor | inhibit | Histone Acetyltransferase | HATs | HAT | GNE-781 | GNE781 | GNE 781 | EpigeneticReaderDomain | Epigenetic Reader Domain | CBP | BRET | BRD41 | BRD4 (1) |
| Inhibitors Related | ABBV-744 | SNDX-5613 | 3-methyl-1,2,3,4-tetrahydroquinazolin-2-one | (+)-JQ-1 | Acetaminophen | 5-Ph-IAA | Manganese chloride (tetrahydrate) | Curcumin | N4-Acetylcytidine | Naphthol AS-E | JQ-1 (carboxylic acid) | Bisdemethoxycurcumin |
| Related Compound Libraries | Reprogramming Compound Library | Histone Modification Compound Library | Bioactive Compound Library | Epigenetics Compound Library | Multi-Target Compound Library | Inhibitor Library | Orally Active Compound Library | PPI Inhibitor Library | Bioactive Compounds Library Max | Fluorochemical Library | Anti-Cancer Compound Library | Anti-Cancer Active Compound Library |
United States
