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Other Sizes |
Targets |
FGFR2 11.8 nM (DC50)
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ln Vitro |
In KATO III, FGFR2 is degraded in a time-dependent manner by LC-MB12 (0.5-10,000 nM, 3-12 hours), with a DC 50 of 11.8 nM [1]. FGFR2 is degraded by 77% in KATO III and 43% in NCI-H1581 by LC-MB12 (100 nM, 6 hours) [1]. With IC50 values of 29.1 nM, 3.7 nM, and 3.2 nM, respectively, LC-MB12 (1-10000 nM, 72 hours) significantly suppresses the growth of KATO III, SNU-16, and NCI-H716 and causes KATO III G0/G1 phase arrest. [1].
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ln Vivo |
In the SNU-16 nude mouse xenograft model, LC-MB12 (20 mg/kg/day, orally, for 15 days) inhibited tumor growth by 63.1%[1]. LC-MB12 (20 mg/kg, oral) is rapidly absorbed in mice (Cmax: 2.6 h) and has oral bioavailability (F: 13%)[1]. LC-MB12 (20 mg/kg, orally, for 30 days) was well tolerated and showed no significant hepatotoxicity or nephrotoxicity in mice[1].
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Cell Assay |
Cell Viability Assay[1]
Cell Types: KATO III, SNU-16, NCI-H716 Tested Concentrations: 0.5 nM, 1.5 nM, 4.3 nM, 13 nM, 41 nM, 123 nM, 370 nM, 1111 nM, 3333 nM, 10000 nM Incubation Duration: 72 h Experimental Results: Inhibited cell growth with IC50s value of 29.1 nM (KATO III); 3.7 nM (SNU-16); 3.2 nM (NCI-H716). Cell Cycle Analysis[1] Cell Types: KATO III Tested Concentrations: 29.1 nM Incubation Duration: 72 h Experimental Results: Induced G0/G1 cycle arrest. Immunofluorescence[1] Cell Types: KATO III Tested Concentrations: 100 nM Incubation Duration: 3 h, 6 h Experimental Results: Promoted FGFR2 was relocated from the cell membrane to intracellular vesicles after treated for 3 or 6 h. Induced receptor internalization and re-localization to the perinuclear section after 6 h treatment. Western Blot Analysis[1] Cell Types: KATO III, NCI-H1581 Tested Concentrations: 0.5 nM, 1.5 nM, 4.3 nM, 13 nM, 41 nM, 123 nM, 370 nM, 1111 nM, 3333 nM, 10000 nM Incubation Duration: 6 h Experimental Results: Degraded FGFR2 with a DC50 of 11.8 nM and D max of ∼80% after 6 h of treatment. demonstrated time -dependent e |
Animal Protocol |
Animal/Disease Models: SNU-16 xenografted in BALB/c-nu (nude) mice [1].
Doses: 20 mg/kg/day Route of Administration: oral administration (po) 15 days Experimental Results: Achieved 63.1% tumor growth inhibition innocuously. Inhibited FGFR phosphorylation and total FGFR2 protein and diminished phosphorylation levels of downstream pPLCγ and ERK1/2. |
References |
[1]. Ma L, et al. Discovery of a Selective and Orally Bioavailable FGFR2 Degrader for Treating Gastric Cancer. J Med Chem. 2023 Jun 8;66(11):7438-7453.
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Molecular Formula |
C43H44CL2N10O8
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Molecular Weight |
899.78
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CAS # |
2828438-38-4
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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HS Tariff Code |
2934.99.9001
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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)
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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
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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
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.1114 mL | 5.5569 mL | 11.1138 mL | |
5 mM | 0.2223 mL | 1.1114 mL | 2.2228 mL | |
10 mM | 0.1111 mL | 0.5557 mL | 1.1114 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.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.