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500mg |
ln Vitro |
EGFR L858R/T790M and EGFR T790M resistant mutants (IC50 values: 0.3 nM and 0.5 nM, respectively) as well as the EGFRexon19del sensitizing mutant (IC50= 0.5 nM) were both successfully suppressed by limertinib in an in vitro kinase experiment. EGFR wild-type (EGFRWT) is the target of ligertinib at 50 nM [1]. When applied to mutant EGFR NSCLC cells, incadratinib shows strong antiproliferative action with IC50 values of 12 nM, 6 nM, and HCC827 against NCI-H1975 (T790M mutation), PC-9, and HCC827 2 nM cells (sensitizing mutation). It also selectively suppresses the development of EGFR mutant cell lines. Nonetheless, in A431, LoVo, and A549 cells (EGFRWT), it demonstrates mild to moderate anti-growth action, with IC50 values ranging from 338 nM to 1541 nM [1]. Even at low dosages (0.1-1 nM), mirtertinib (0.1-100 nM) suppresses the phosphorylation of EGFR tyrosine residue 1068 and its downstream signaling proteins AKT and ERK in NCI-H1975 cells (EGFRL858R/T790M). Moreover, at dosages of 10 to 100 nM, limertinib suppresses p-EGFR in EGFR WT A431 cells along with p-Akt and p-erk [1].
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ln Vivo |
Limertinib (oral gavage; 5-20 mg/kg; once daily; 21 days) strongly suppressed tumor development, with a tumor growth inhibition (TGI) rate of 85.7%, and administration of 10 mg/kg Limertinib resulted in a dramatic tumor shrinkage TGI rate It is 99.3% and has similar efficacy to Osimertinib [1].
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Animal Protocol |
Animal/Disease Models: BALB/cA nude mice[1]
Doses: 5-20 mg/kg Route of Administration: po (oral gavage); 5-20 mg/kg; one time/day; 21 days Experimental Results: Well tolerated by animals, no observed Weight loss demonstrated profound and selective antitumor efficacy and diminished TGI rates. Dramatically inhibits the phosphorylation of EGFR L858R/T790M and AKT in tumor tissues. |
References |
[1]. Tao Zhang, et al. Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance. Mol Cancer. 2020 May 13;19(1):90.
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Molecular Formula |
C29H32CLN7O2
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Molecular Weight |
546.072
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CAS # |
1934259-00-3
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SMILES |
N(C1C=C(OC)C(NC2=NC=C(Cl)C(NC3C=CC4C=CC=CC=4C=3)=N2)=CC=1NC(=O)C=C)(C)CCN(C)C
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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) |
DMSO : ~41.67 mg/mL (~76.31 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8313 mL | 9.1563 mL | 18.3127 mL | |
5 mM | 0.3663 mL | 1.8313 mL | 3.6625 mL | |
10 mM | 0.1831 mL | 0.9156 mL | 1.8313 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.