GNE-049

SKU: orb1707262

Description

GNE-049 is a potent and selective small molecule inhibitor of CREB-binding protein (CBP), demonstrating an IC50 of 1.1 nM. It effectively suppresses BRET/BRD4 activity and inhibits prostate cancer cell proliferation in both in vitro and in vivo research models.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1936421-41-8
• MW: 510.58
• Purity: 98.67% (May vary between batches)
• Formula: C₂₇H₃₂F₂N₆O₂
• SMILES: O=C(N1CC=2C(=NN(C2CC1)C3CCOCC3)N4C=5C=C(C(=CC5CCC4)C=6C=NN(C6)C)C(F)F)C
• Target: Epigenetic Reader Domain,Histone Acetyltransferase
• Solubility: DMSO:80 mg/mL (156.68 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.46 mM)

Bioactivity

• Target IC50:
  MV-4-11 cells:14 nM (EC50)|HEK293 cells:15 nM
• In Vivo:
  GNE-049 shows acceptable PK in mouse, rat, dog, and monkey. GNE-049 is further evaluated in a rat single dose (30-250 mg/kg QD) toxicokinetic study. GNE-049 is selective for CBP/P300 and, importantly, quite selective (3820-fold) over BRD4(1), which revealed from the Determination of potency versus a selection of bromodomains. Furthermore, at the 250 mg/kg dose level, the ratio of the unbound drug concentration in the brain to unbound drug concentration in plasma (Kp,uu) 3 h post-dose is determined to be 0.43, indicating that GNE-049 is penetrating into the CNS and potentially resulting in the observed toxicity.
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• In Vitro:
  GNE-049 performs well in BRET cell assays and, in an orthogonal targeted assay, inhibits MYC expression (MV4-11 cell line) with an EC50 of 14 nM. CBPD-409 induced strong degradation of CBP/p300 by DC 500.2-0.4 nM and exhibited strong antiproliferative effects with IC50 of 1.2-2.0 nM in VCaP, LNCaP, and 22Rv1 AR+ prostate cancer cell lines.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BRD41, BRET, CBP, Epigenetic Reader Domain, EpigeneticReaderDomain, GNE049, GNE-049, GNE 049

Compound Identifiers

PubChem CID

121373418