Physicochemical Properties
| Molecular Formula | C22H20CLF2N3O3 |
| Molecular Weight | 447.86 |
| Exact Mass | 447.116 |
| CAS # | 2832159-79-0 |
| Related CAS # | (2S,4R)-DS89002333;(R)-DS89002333 |
| PubChem CID | 168008735 |
| Appearance | White to off-white solid powder |
| Density | 1.411±0.06 g/cm3(Predicted) |
| Boiling Point | 680.3±55.0 °C(Predicted) |
| LogP | 3.2 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 31 |
| Complexity | 633 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | COC1=C(C=C2C=CN=C(C2=C1)F)C(=O)N[C@H]([C@@H]3C[C@H](CN3)O)C4=CC(=C(C=C4)F)Cl |
| InChi Key | KALMTELCNYQBGB-MJWYBRSISA-N |
| InChi Code | InChI=1S/C22H20ClF2N3O3/c1-31-19-9-14-11(4-5-26-21(14)25)6-15(19)22(30)28-20(18-8-13(29)10-27-18)12-2-3-17(24)16(23)7-12/h2-7,9,13,18,20,27,29H,8,10H2,1H3,(H,28,30)/t13-,18+,20+/m1/s1 |
| Chemical Name | N-[(S)-(3-chloro-4-fluorophenyl)-[(2S,4R)-4-hydroxypyrrolidin-2-yl]methyl]-1-fluoro-7-methoxyisoquinoline-6-carboxamide |
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | PRKACA 0.3 nM (IC50) |
| ln Vitro | In NIH/3T3 cells, DS89002333 (0.001, 0.01, 0.1, 1, 10 µM; 30 min) dose-dependently suppresses CREB phosphorylation (CREB phosphorylation status as a measure of intracellular PRAKACA inhibitory activity)[1]. |
| ln Vivo | In an NIH/3T3-fusion allograft model, DS89002333 (12.5, 50 mg/kg; po; twice daily for 5 days) exhibits anti-tumor activity[1]. In the FL-HCC PDX xenograft model, DS89002333 (3, 30 mg/kg; po; twice daily for 22 days) exhibits strong anti-tumor activity[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: NIH/3T3 cells Tested Concentrations: 0.001, 0.01, 0.1, 1, 10 µM Incubation Duration: 30 min Experimental Results: demonstrated a dose-dependent decrease in phosphorylation of CREB, with an IC50 of 50 nM. |
| Animal Protocol |
Animal/Disease Models: Female nude mice (NIH/3T3-fusion allograft model)[1]. Doses: 12.5, 50 mg/kg Route of Administration: Oral administration , twice daliy for 5 days. Experimental Results: demonstrated anti-tumor activity without body weight loss. Animal/Disease Models: Female NOD SCID (severe combined immunodeficient) mouse (FL-HCC PDX xenograft model)[1]. Doses: 3, 30 mg/kg Route of Administration: Oral administration , twice daliy for 22 days. Experimental Results: Significant inhibited tumor in mice, and demonstrated temporary body weight loss (at 30 mg/kg), but this resolved following continuous dosing. |
| References |
[1]. ovel protein kinase cAMP-Activated Catalytic Subunit Alpha (PRKACA) inhibitor shows anti-tumor activity in a fibrolamellar hepatocellular carcinoma model. Biochem Biophys Res Commun. 2022 Sep 17;621:157-161. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (223.28 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.58 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 (5.58 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 (5.58 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 | 2.2328 mL | 11.1642 mL | 22.3284 mL | |
| 5 mM | 0.4466 mL | 2.2328 mL | 4.4657 mL | |
| 10 mM | 0.2233 mL | 1.1164 mL | 2.2328 mL |