Physicochemical Properties
| Molecular Formula | C26H22FN5O2 |
| Exact Mass | 455.18 |
| Elemental Analysis | C, 68.56; H, 4.87; F, 4.17; N, 15.38; O, 7.02 |
| CAS # | 2729996-45-4 |
| Related CAS # | 2729996-45-4 |
| PubChem CID | 155920128 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 3.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 34 |
| Complexity | 867 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | SXCTZLXYGLXXRY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H22FN5O2/c1-15-8-21(27)22(31-24(33)16-6-5-7-19(10-16)26(2,3)14-28)11-20(15)17-9-18-13-30-32(4)25(34)23(18)29-12-17/h5-13H,1-4H3,(H,31,33) |
| Chemical Name | 3-(2-cyanopropan-2-yl)-N-[2-fluoro-4-methyl-5-(7-methyl-8-oxopyrido[2,3-d]pyridazin-3-yl)phenyl]benzamide |
| Synonyms | GNE 9815; GNE-9815; GNE9815 |
| 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
| Targets | CRAF (Ki = 0.062 nM); Braf (Ki = 0.19 nM) |
| ln Vitro | GNE-9815 exhibits synergistic activity in KRAS mutant A549 and HCT116 cancer cells in combination with the MEK inhibitor Cobimetinib[1]. |
| ln Vivo |
GNE-9815 (15 mg/kg; p.o., single) exhibits synergistic MAPK pathway modulation when combined with the MEK inhibitor Cobimetinib in an HCT116 xenograft mouse model[1]. GNE-9815 5 mg/kg; p.o.; single) exhibits low blood clearance, a moderate volume of distribution, and a brief half-life, while GNE-9815 (5 mg/kg; p.o.; single) exhibits good oral bioavailability[1]. |
| Animal Protocol |
Female NCR nude mice (6 to 8-week-old; 24-26 g; HCT116 xenograft mice model)[1]. 15 mg/kg Intravenous injection or oral administration; single. |
| References |
[1]. Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a Pyridopyridazinone pan-RAF Kinase Inhibitor. ACS Med Chem Lett. 2021 Apr 21;12(5):791-797. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~109.8 mM) Ethanol: ~5 mg/mL (11.0 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.49 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 25.0 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: ≥ 2.5 mg/mL (5.49 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 25.0 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: ≥ 2.5 mg/mL (5.49 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 25.0 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.) |