Physicochemical Properties
| Molecular Formula | C20H16F3N7OS |
| Molecular Weight | 459.45 |
| Exact Mass | 459.109 |
| Elemental Analysis | C, 52.28; H, 3.51; F, 12.41; N, 21.34; O, 3.48; S, 6.98 |
| CAS # | 877874-85-6 |
| PubChem CID | 53328059 |
| Appearance | White to off-white solid powder |
| LogP | 5.123 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 32 |
| Complexity | 596 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC(C1C=C(NC2NC(C3C=CC(OC4C=C(N)N=C(SC)N=4)=CC=3)=NN=2)C=CC=1)(F)F |
| InChi Key | CMYHZFCJPORPHY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H16F3N7OS/c1-32-19-26-15(24)10-16(27-19)31-14-7-5-11(6-8-14)17-28-18(30-29-17)25-13-4-2-3-12(9-13)20(21,22)23/h2-10H,1H3,(H2,24,26,27)(H2,25,28,29,30) |
| Chemical Name | 2-methylsulfanyl-6-[4-[3-[3-(trifluoromethyl)anilino]-1H-1,2,4-triazol-5-yl]phenoxy]pyrimidin-4-amine |
| Synonyms | KG5; KG 5; KG-5 |
| HS Tariff Code | 2934.99.03.00 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | KG5 (compound 6) has an EC50 value of 0.59 μM for vascular smooth muscle cells (VSMC) and 0.54 μM for endothelial cells, respectively, which means that it reduces their viability [1]. Compound 6 does not impact S259, but it specifically prevents S338 phosphorylation[1]. With Kd of 300 and 520 nM, respectively, and Flt3 and KIT of 52 and 170 nM, respectively, KG5 (compound 6) exclusively inhibits PDGFRα and β [1]. Compound 6 (KG5; 5 μM) prevents bFGF- or VEGF-stimulated endothelial cells from phosphorylating MEK and ERK [1]. |
| ln Vivo | In an orthotopic renal cell carcinoma model, KG5 (Compound 6; 100 mg/kg; oral; daily; for 26 days) therapy inhibits tumor growth [1]. Comparing KG5 (Compound 6; 50 mg/kg; intraperitoneal; twice daily) therapy to vehicle controls (mouse injection of Matrigel containing bFGF) revealed full inhibition of angiogenesis. The area under the concentration-time curve (AUC0–12h) was 14.7 μg·h/mL, T1/2 was 11.5 h, and Cmax was 3.6 μg/mL according to pharmacokinetic studies of the dosage and formulation utilized for KG5[1]. In zebrafish development, KG5 (Compound 6; 1 μM) interferes with the last stages of angiogenesis [1]. |
| Animal Protocol |
Animal/Disease Models: Male Nu/nu (nude) mice were injected with SN12C-RFP cells [1] Doses: 100 mg/kg Route of Administration: Oral; daily; continued for 26 days Experimental Results: Prevented tumor growth in the orthotopic renal cell carcinoma model. |
| References |
[1]. Disruption of angiogenesis and tumor growth with an orally active drug that stabilizes the inactive state of PDGFRbeta/B-RAF. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4299-304. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~217.65 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.44 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 | 2.1765 mL | 10.8826 mL | 21.7652 mL | |
| 5 mM | 0.4353 mL | 2.1765 mL | 4.3530 mL | |
| 10 mM | 0.2177 mL | 1.0883 mL | 2.1765 mL |