c-Met-IN-22 (compound 51am) is an orally available c-Met inhibitor with an IC50 value of 2.54 nM. c-Met-IN-22 has antiproliferative and antitumor activities. c-Met-IN-22 can induce cell apoptosis.

Physicochemical Properties

Molecular Formula	C21H10CL3F2N3O2S
Molecular Weight	512.74
Appearance	Typically exists as solid at room temperature
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	c-Metwild type 2.54 nM (IC50) c-MetH1094R 93.6 nM (IC50) c-MetD1228H 29.4 nM (IC50) c-MetY1230H 45.8 nM (IC50) c-MetY1235D 54.2 nM (IC50) c-MetM1250T 26.5 nM (IC50) c-Metkit 4.94 nM (IC50) c-MetRon 3.83 nM (IC50) c-MetPDGFRα 425 nM (IC50) c-MetPDGFRβ 513 nM (IC50) c-MetVEGFR-2 527 nM (IC50) c-MetFit-3 6.12 nM (IC50) c-MetFit-4 276 nM (IC50)
ln Vitro	c-Met-IN-22 has anti-proliferative activity in cells MNK-45, A-549, HT-29, MDA-MB-231, HUVEC, and FHC, with IC50 values of 0.092, 0.83, 0.68, 3.94, 2.54, and 8.63 μM[1]. c-Met-IN-22 still has inhibitory effects on mutants H1094R, D1228H, Y1230H, Y1235D and M1250T, with IC50 values of 93.6, 29.4, 45.8, 54.2 and 26.5 nM respectively [1]. c-Met-IN-22 (0, 2.5, 5.0 and 10.0 μM; 24 h) dose-dependently inhibits the phosphorylation of c-Met in MKN-45 [1]. c-Met-IN-22 (0.4, 0.8 and 1.2 μM; 24 h) induces MNK-45 cell cycle arrest in the G2 phase and apoptosis in a dose-dependent manner [1].
ln Vivo	c-Met-IN-22 (10 mg/kg; oral; single dose) showed good oral bioavailability (F=69%) in BALB/c mice, with an elimination half-life of 5.6 hours and a clearance rate of 0.87 L/h•kg [1]. The elimination half-life of c-Met-IN-22 (1.5 mg/kg, intravenous injection) in BALB/c mice was 3.2 hours [1]. Pharmacokinetic analysis of c-Met-IN-22 in BALB/c mice [1] Route Dose (mg/kg) AUC0→∞ (μg·h/mL) T1/2 (h) Tmax (h) Cmax (ng/mL) Cl (L/h·kg) F (%) iv 1.5mg/kg 2.5 3.2 / 552 0.6 / po 10mg/kg 11.5 5.6 4.1 1756 / 69
Cell Assay	Apoptosis Analysis[1] Cell Types: MNK- 45 cells Tested Concentrations: 0.4, 0.8, 1.2 μM Incubation Duration: 24 h Experimental Results: Induced cell apoptosis in a dose-dependent manner. Cell Cycle Analysis[1] Cell Types: MNK- 45 cells Tested Concentrations: 0.4, 0.8, 1.2 μM Incubation Duration: 24 h Experimental Results: Induced cell cycle arrest at G2 phase in a dose-dependent manner. Western Blot Analysis[1] Cell Types: MNK- 45 cells Tested Concentrations: 0, 2.5, 5, 10 μM Incubation Duration: 24 h Experimental Results: Inhibited c-Met phosphorylation in a dose-dependent manner.
Animal Protocol	Animal/Disease Models: Pharmacokinetic Analysis in BALB/c mice Doses: p.o.10 mg/kg; i.v. 1.5 mg/kg Route of Administration: Intravenous (i.v.) injection, Oral administration (p.o.) Experimental Results: Characterised good maximum concentration, plasma exposure and elimination half-time in pharmacokinetics.
References	[1].Design, synthesis, and biological evaluation of thiazole/thiadiazole carboxamide scaffold-based derivatives as potential c-Met kinase inhibitors for cancer treatment. J Enzyme Inhib Med Chem. 2023 Dec;38

Solubility Data

Solubility (In Vitro)

Typically soluble in DMSO (e.g. 10 mM)

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	1.9503 mL	9.7515 mL	19.5031 mL
	5 mM	0.3901 mL	1.9503 mL	3.9006 mL
	10 mM	0.1950 mL	0.9752 mL	1.9503 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.