Physicochemical Properties
| Molecular Formula | C22H16FN7O2S |
| Molecular Weight | 461.471545219421 |
| Exact Mass | 461.107 |
| CAS # | 1637658-98-0 |
| PubChem CID | 86302574 |
| Appearance | White to off-white solid powder |
| LogP | 3 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 33 |
| Complexity | 752 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1C2C(=CC(SC3N4C(=NN=3)C(F)=CC(C3=CN(C)N=C3)=C4)=CC=2)C2OCC(=O)N(C)C=2C=1 |
| InChi Key | MFEXYTURXUZOID-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H16FN7O2S/c1-28-9-13(7-25-28)12-5-16(23)21-26-27-22(30(21)10-12)33-14-3-4-17-15(6-14)20-18(8-24-17)29(2)19(31)11-32-20/h3-10H,11H2,1-2H3 |
| Chemical Name | 9-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-4-methyl-[1,4]oxazino[3,2-c]quinolin-3-one |
| 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 | Dalmelitinib (compound 4 d) binds to the ATP-binding domain of c-Met kinase and exhibits 2.9 nM IC50 selective inhibitory action against c-Met [1]. With IC50 values ranging from 6 nM to 33 nM, damelitinib (about 0-1 μM, 3 days) reduces cell proliferation in a variety of c-Met oncogene-amplified cancer cell lines [1]. In HCCLM3 cells, damelitinib (0.1–1 μM, 6–24 h) strongly increases tyrosine kinase (MET) phosphorylation and either totally or partially suppresses ERK and AKT phosphorylation downstream [1]. |
| ln Vivo | Dalmelitinib (compound 4 d, intragastric injection, 10-60 mg/kg) effectively suppressed tumor growth in MKN-45 tumor xenograft nude mice in a dose-dependent manner [1]. Damatinib (given by gavage, single dose 5 mg/kg) showed high blood concentration, extended half-life and mean residence time, and low clearance rate in BALB/c nude mice [1]. Dalmelitinib revealed significant no-observed adverse effect levels (NOAELs) in long-term toxicity (225 mg/kg/day) and acute toxicity (600 mg/kg/day) in mice [1]. |
| Cell Assay |
Cell proliferation experiment [1] Cell Types: C-Met oncogene amplified cancer cells: SNU-5, HCCLM3, MHCC97-H, MHCC97-L, MKN-45, NCI-H1993. Cancer cells without C-Met oncogene amplification: Huh-7, NCI-N87, NCI-1975, A549. Tested Concentrations: approximately 0-1μM. Incubation Duration: 3 days Experimental Results: IC50: 33 nM (HCCLM3), 6 nM (MHCC97-H, MKN-45), 7 nM (MHCC97-L), 14 nM (NCI-H1993), 2 nM (SNU-5) ;Other cells: >1000 nM. Western Blot Analysis [1] Cell Types: C-Met oncogene amplified cancer cells: SNU-5, HCCLM3, MHCC97-H, MHCC97-L, MKN-45, NCI-H1993. Cancer cells without C-Met oncogene amplification: Huh-7, NCI-N87, NCI-1975, A549. Tested Concentrations: 0.1, 0.3, 1 μM Incubation Duration: 6-24 h Experimental Results: Dramatically induced tyrosine kinase (MET) phosphorylation, partially inhibited AKT downstream phosphorylation, and completely inhibited ERK downstream phosphorylation. |
| Animal Protocol |
Animal/Disease Models: MKN-45 tumor xenograft nude mice [1] Doses: 10, 30, 60 mg/kg Route of Administration: intragastric (po) (po)administration Experimental Results: Inhibited tumor growth, the inhibition rates were 29.5% (10 mg/kg), 34.2 % (10 mg/kg). 30 mg/kg) and 61.4% (60 mg/kg). Animal/Disease Models: BALB/c nude mice (pharmacokinetic/PK/PK determination) [1] Doses: single dose 5 mg/kg Route of Administration: intragastric (po) (po)administration Experimental Results: pharmacokinetic/PK/PK characteristics of dametinib (compound 4d) Compound Cmax (ng/mL) AUC (ng/mL/h) t1/2 (h) MRT (h) CL/F (mL/min/kg) Vz/F Damitinib 8628 122487 5.55 9.10 0.68 327 |
| References |
[1]. Synthesis and biological evaluation of new [1,2,4]triazolo[4,3-a]pyridine derivatives as potential c-Met inhibitors. Bioorg Med Chem. 2016 Aug 15;24(16):3483-93. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1670 mL | 10.8349 mL | 21.6699 mL | |
| 5 mM | 0.4334 mL | 2.1670 mL | 4.3340 mL | |
| 10 mM | 0.2167 mL | 1.0835 mL | 2.1670 mL |