GNE-781

SKU: orb1308265

Description

GNE-781 is a potent and selective CBP inhibitor with an IC50 of 0.94 nM, also showing activity against BRET and BRD4(1). This small molecule is a valuable chemical probe for epigenetic research, enabling the study of CBP/p300 function in cancer models and transcriptional regulation in both cellular and biochemical assays.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1936422-33-1
• MW: 525.59
• Purity: 99.92% (May vary between batches)
• Formula: C₂₇H₃₃F₂N₇O₂
• SMILES: CNC(=O)N1CCc2c(C1)c(nn2C1CCOCC1)N1CCCc2cc(-c3cnn(C)c3)c(cc12)C(F)F
• Target: Epigenetic Reader Domain,Histone Acetyltransferase
• Solubility: Ethanol:95 mg/mL (180.75 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.81 mM);DMSO:95 mg/mL (180.75 mM)

Bioactivity

• Target IC50:
  BRD41:5100 nM|BRET:6.2 nM|CBP:0.94 nM
• 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.
• 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)) .

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BRD4 (1), BRD41, CBP, BRET, inhibit, GNE781, GNE-781, GNE 781, EpigeneticReaderDomain, Epigenetic Reader Domain, Inhibitor, HATs, HAT, Histone Acetyltransferase

Compound Identifiers

PubChem CID

132275066