Physicochemical Properties
| Molecular Formula | C25H24FIN6O5S |
| Molecular Weight | 666.463139533997 |
| Exact Mass | 666.055 |
| CAS # | 2666940-97-0 |
| PubChem CID | 154700547 |
| Appearance | White to light yellow solid powder |
| LogP | 2.9 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 39 |
| Complexity | 1230 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(NC1=CC=CC(N2C3=C(C)C(=O)N(C)C(NC4=CC=C(I)C=C4F)=C3C(=O)N(C3CC3)C2=O)=C1)(NC)(=O)=O |
| InChi Key | DNNMBAWCLGMMRJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H24FIN6O5S/c1-13-21-20(22(31(3)23(13)34)29-19-10-7-14(27)11-18(19)26)24(35)33(16-8-9-16)25(36)32(21)17-6-4-5-15(12-17)30-39(37,38)28-2/h4-7,10-12,16,28-30H,8-9H2,1-3H3 |
| Chemical Name | 3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-1-[3-(methylsulfamoylamino)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione |
| 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 | MEK1 MEK2 |
| ln Vitro | On KSR-bound MEK, trametiglue preserves trametinib's potent binding ability and residence duration [1]. In contrast to trametinib, but akin to avitometinib, trametiglue improves the relationship between endogenous BRAF and MEK1 [1]. Direct binding tests show that metetipleniglue (1 μM) is very selective for MEK1 and MEK2. Trametiglue exhibits a high degree of selectivity when it comes to a class of active kinases that either directly phosphorylate MEK1 or MEK2 substrates or prevent upstream kinases from doing so [1]. HCT116, A375, A549, and SK-MEL-239 cells' viability is inhibited by metamiglue (5 days) with IC50 values of 0.07, 0.07, 0.12, and 0.47 nM, respectively[1]. More potently than trametinib, trametiglue (10 nM; 10 days) suppresses the development of colonies in cancer cells with mutant BRAF and KRAS [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: SK-MEL-239, HCT116, A549 and A375 Tested Concentrations: Incubation Duration: 5 days Experimental Results: demonstrated IC50s of 0.47, 0.07, 0.12 and 0.07 nM against SK-MEL-239, HCT116, A549 and A375 cells, respectively. Western Blot Analysis[1] Cell Types: A549, HCT-116, A375 and SK-MEL-239 Tested Concentrations: 0.4, 0.8, 1.6, 3.1, 6.25, 12.5, 25 and 50 nM Incubation Duration: 1 h Experimental Results: Inhibited the expression of pERK. And the effect was better than Trametinib. |
| References |
[1]. Structural basis for the action of the drug trametinib at KSR-bound MEK. Nature. 2020 Dec;588(7838):509-514. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (150.05 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5005 mL | 7.5023 mL | 15.0047 mL | |
| 5 mM | 0.3001 mL | 1.5005 mL | 3.0009 mL | |
| 10 mM | 0.1500 mL | 0.7502 mL | 1.5005 mL |