Physicochemical Properties
| Molecular Formula | C23H23CL2N5O5 |
| Molecular Weight | 520.37 |
| Exact Mass | 519.107 |
| CAS # | 1628793-01-0 |
| PubChem CID | 90436886 |
| Appearance | White to off-white solid powder |
| LogP | 2.9 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 35 |
| Complexity | 831 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | O(C1=CC(OC)=C(Cl)C(C2=CC3C(N(C)C2=O)=NC(N[C@H]2[C@@H](NC(C=C)=O)COC2)=NC=3)=C1Cl)C |
| InChi Key | ZIJVLVUPDVUSMA-UONOGXRCSA-N |
| InChi Code | InChI=1S/C23H23Cl2N5O5/c1-5-17(31)27-13-9-35-10-14(13)28-23-26-8-11-6-12(22(32)30(2)21(11)29-23)18-19(24)15(33-3)7-16(34-4)20(18)25/h5-8,13-14H,1,9-10H2,2-4H3,(H,27,31)(H,26,28,29)/t13-,14+/m0/s1 |
| Chemical Name | N-[(3R,4S)-4-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]oxolan-3-yl]prop-2-enamide |
| 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 | FGFR4 6.5 nM (IC50) FGFR2 505 nM (IC50) |
| ln Vivo | FGFR4-IN-5 (oral gavage; 10 mg/kg; single dose) reveals a high Cmax, low clearance, the Cmax values are 423 ng/ml, 588 ng/ml, and 2820 ng/ml in mice, rat and cynamolgus monkey, respectively. And the oral bioavailability are 20, 12, and 27% in mouse, rat, and cyno, respectively[1]. FGFR4-IN-5 (oral gavage; 100 mg/kg; twice daily; 28 days) exhibits strong antitumor activity in an orthotopic Hep3B HTX model[1]. FGFR4-IN-5 (oral gavage; 10, 30, and 100 mg/kg; twice daily; 11 days) results in dose-dependent growth inhibition of resistant tumors. Tumor Regression is observed at 30 and 100 mg/kg, with %ΔT/ΔC of 67% and 70%, respectively. However, treatment with sorafenib at 100 mg/kg once daily does not provide any benefit in vivo[1]. |
| Animal Protocol |
Animal/Disease Models: Hep3B cell bearing mice model[1] Doses: 100 mg/kg Route of Administration: Oral gavage; 100 mg/kg; twice (two times) daily; 28 days Experimental Results: Resulted in tumor regression and sustained growth inhibition. Animal/Disease Models: Sorafenib-resistant tumors established to mice bearing Huh7 tumors[1] Doses: 10, 30, and 100 mg/kg Route of Administration: Oral gavage; 10, 30, and 100 mg/kg; twice (two times) daily; 11 days Experimental Results: Resulted in dose-dependent growth inhibition of resistant tumors. |
| References |
[1]. Discovery of Selective, Covalent FGFR4 Inhibitors with Antitumor Activity in Models of Hepatocellular Carcinoma. ACS Med Chem Lett. 2020 Mar 6;11(10):1899-1904. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (192.17 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 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 (4.80 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9217 mL | 9.6085 mL | 19.2171 mL | |
| 5 mM | 0.3843 mL | 1.9217 mL | 3.8434 mL | |
| 10 mM | 0.1922 mL | 0.9609 mL | 1.9217 mL |