KRC-00715 is an orally available inhibitor of c-Met (IC50 of 9.0 nM) with high selectivity. KRC-00715 specifically inhibits the growth of c-Met high-expressing cell lines by inducing G1/S arrest in gastric cancer cells, reducing downstream signaling including Akt and Erk as well as c-Met activity. The cytotoxicity IC50 of KRC-00715 in the gastric cancer cell line Hs746 is 39 nM, and it only inhibits the proliferation of cell lines that highly express c-Met. KRC-00715 reduces tumor size in the Hs746T xenograft mouse model.

Physicochemical Properties

Molecular Formula	C25H25F3N8O3
Molecular Weight	542.51
CAS #	2079853-72-6
Appearance	Typically exists as solids 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

ln Vitro	KRC-00715 has a cytotoxicity IC50 of 39 nM and is an excellent c-Met inhibitor [1]. KRC-00715 (8, 40, 200, 1000 nM; 3 h; Hs746T, AGS) inhibits c-Met autophosphorylation, and the inhibition of c-Met activity mainly contributes to the inhibition of cell proliferation [1]. KRC-00715 is active in c-Met high-expressing cell lines with an IC50 value of 39 nM in Hs746T cells, and inhibits c-Met autophosphorylation, Akt and Erk phosphorylation in high-expressing cell lines [1]. KRC-00715 (30 nM and 300 nM) has a more significant inhibitory effect on SNU-5 G1/S than SNU-1, with values of 72.53 and 64.54 at 30 nM and 73.62 and 83.64 at 300 nM [1].
ln Vivo	KRC-00715 (50mg/kg; Oral gavage (p.o.); 每日一次; 10 天) 抑制在裸鼠异种移植 Hs746T 肿瘤体积增加[1]。
Cell Assay	Western Blot Analysis[1] Cell Types: Hs746T, SNU-638, SNU-620, AGS, SNU -1, MKN-1 Concentration: 8, 40, 200, 1000 nM Incubation Duration: 3 h Experimental Results: Inhibited c-Met autophosphorylation by 70%, inhibited the proliferation of HS746T cells, and inhibited the phosphorylation of Akt and ERK in overexpressed cell lines, with low expression unaffected. Cell Cycle Analysis[1] Cell Types: SNU1, SNU5 Concentration: 30nM, 300nM Incubation Duration: 24 h Experimental Results: Induced SNU5 arrest in G1/S phase and no cell cycle arrest was found in SNU1. Induced G1/S arrest of c-met overexpressing cells to inhibit cell proliferation. Cell Cytotoxicity Assay[1] Cell Types: Hs746T Concentration: Incubation Duration: 3 days Experimental Results: Showed the cytotoxic IC50 of HS746 cell line was 39 nm. Cell Cytotoxicity Assay[1] Cell Types: SNU-1, SNU-5, SNU-16, SNU-216, SNU-484, SNU-601, SNU-620, SNU-638, SNU-668, MKN-1, MKN-28, MKN-74, NCI-N87, KATOⅢ, AGS, SNU-719, MKN-45, Hs746T Concentration: 0.0001-1 μM Incubation Duration: 72 h Experimental Results: Showed the IC50 value was less than or equal to 10 nM in c-Met overexpressing cell lines and no toxic effect in low-expression cell lines.
Animal Protocol	Animal/Disease Models: Nude mouse Hs746T xenograft model[1]. Doses: 50 mg/kg Route of Administration: oral gavage (p.o.)；once daily; 10 days Experimental Results: Reduced the tumor volume, and the weight of mice did not reduce.
References	[1]. Chi Hoon Park, et al. Novel c-Met inhibitor suppresses the growth of c-Met-addicted gastric cancer cells.BMC Cancer. 2016 Jan 22:16:35.

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	1.8433 mL	9.2164 mL	18.4328 mL
	5 mM	0.3687 mL	1.8433 mL	3.6866 mL
	10 mM	0.1843 mL	0.9216 mL	1.8433 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.