Physicochemical Properties
| Molecular Formula | C30H37N3O5 |
| Molecular Weight | 519.63 |
| Exact Mass | 519.273 |
| CAS # | 2578876-75-0 |
| PubChem CID | 155471755 |
| Appearance | White to off-white solid powder |
| LogP | 4.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 38 |
| Complexity | 741 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1C(C)=C(C=CC=1OC)C1C2=CC(=C(OC)C=C2CCN1C(NCC)=O)OCCC1C=CC(OC)=C(N)C=1 |
| InChi Key | WKOOIGPIJNQBPY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C30H37N3O5/c1-6-32-30(34)33-13-11-21-17-27(37-5)28(38-14-12-20-7-10-26(36-4)25(31)16-20)18-24(21)29(33)23-9-8-22(35-3)15-19(23)2/h7-10,15-18,29H,6,11-14,31H2,1-5H3,(H,32,34) |
| Chemical Name | 7-[2-(3-amino-4-methoxyphenyl)ethoxy]-N-ethyl-6-methoxy-1-(4-methoxy-2-methylphenyl)-3,4-dihydro-1H-isoquinoline-2-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 |
| 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 | KRAS mutant tumor cells are inhibited in their ability to proliferate by KRAS inhibitor-10 (0.1-50μM; 72 hours). KRAS inhibitor-10 specifically targets A549, a lung cancer cell line with an oncogenic KRasG12S mutation, and H358, a non-small cell line with the same mutation. The KRasG12C oncogenic mutation in lung cancer cell line, the KRasG12D oncogenic mutation in pancreatic epithelioid carcinoma cell line PANC-1, and the KRasG12A oncogenic mutation in myeloma cell line RPMI all had IC50 values of 0.2 μM, 0.2 μM, 0.1 μM, and 0.8 μM, respectively, for cell proliferation [1]. In the 3D CellTiter-GloTM cell viability experiment of NIH-H358 cells, KRAS inhibitor-10 (0-1 μM, 7 days) inhibited cell viability with an IC50 value of 0.413 μM [1]. |
| ln Vivo | KRAS inhibitor-10 (oral; 20 mg/kg; BID; 27 days) is safe and well tolerated in pregnant mice. KRAS inhibitor-10 showed substantial oral anticancer efficacy in vivo. The tumor growth inhibition (TGI) value of KRAS inhibitor 10 is 48.22% [1]. |
| Animal Protocol |
Animal/Disease Models: NCr nude mice subcutaneously (sc) (sc) injected NCI-H358 human lung cancer model [1] Doses: 20 mg/kg Route of Administration: oral; Route of Administration: oral. 20 mg/kg; bid; 27-day Experimental Results: Tumor volume in tumor-bearing mice diminished and anti-tumor effects were demonstrated. |
| References |
[1]. Tetrahydroisoquinoline compounds. Patent wo2021002165. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~192.44 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.81 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 (4.81 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 | 1.9244 mL | 9.6222 mL | 19.2445 mL | |
| 5 mM | 0.3849 mL | 1.9244 mL | 3.8489 mL | |
| 10 mM | 0.1924 mL | 0.9622 mL | 1.9244 mL |