GNE-207 is a novel, potent, selective and orally bioavailable inhibitor of the bromodomain of CBP. It has excellent CBP potency (CBP IC50 = 1 nM, MYC EC50 = 18 nM), a selectively index of >2500-fold against BRD4(1), and exhibits a good pharmacokinetic profile.
Physicochemical Properties
| Molecular Formula | C29H30N6O3 |
| Molecular Weight | 510.586905956268 |
| Exact Mass | 510.237 |
| CAS # | 2158266-58-9 |
| PubChem CID | 132186469 |
| Appearance | White to off-white solid powder |
| LogP | 2 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 38 |
| Complexity | 852 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O1CCC(CC1)N1C2CCN(C(C)=O)CC=2C(C2C=CC=C3C=C(C4C=NC(C(NC)=O)=CC=4)N=CC=23)=N1 |
| InChi Key | MUJXZEDIWKGKQD-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C29H30N6O3/c1-18(36)34-11-8-27-24(17-34)28(33-35(27)21-9-12-38-13-10-21)22-5-3-4-19-14-26(32-16-23(19)22)20-6-7-25(31-15-20)29(37)30-2/h3-7,14-16,21H,8-13,17H2,1-2H3,(H,30,37) |
| Chemical Name | 5-(8-(5-Acetyl-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)isoquinolin-3-yl)-N-methylpicolinamide |
| Synonyms | GNE-207; GNE207; GNE 207 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | GNE-207 is an orally accessible, effective, and selective CBP bromodomain inhibitor that has an IC50 of 1 nM and a selectivity index of >2500-fold against BRD4 (1) (IC50, 3.1 μM) [1]. GNE-207 exhibits exceptional CBP efficacy in MV-4-11 cells, with an EC50 of 18 nM for MYC expression [1]. |
| ln Vivo | GNE-207 (5 mg/kg) has a respectable oral bioavailability and a moderate PK clearance [1]. |
| References |
[1]. Design and synthesis of a biaryl series as inhibitors for the bromodomains of CBP/P300. ioorg Med Chem Lett. 2018 Jan 1;28(1):15-23. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~200 mg/mL (~391.70 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (9.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (9.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9585 mL | 9.7926 mL | 19.5852 mL | |
| 5 mM | 0.3917 mL | 1.9585 mL | 3.9170 mL | |
| 10 mM | 0.1959 mL | 0.9793 mL | 1.9585 mL |