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Purity: ≥98%
| Targets |
Olafertinib targets the epidermal growth factor receptor (EGFR) tyrosine kinase, specifically and covalently binding to and inhibiting specific EGFR mutations. It has high selectivity for mutant EGFR (L858R/T790M, del19) over wild-type EGFR. The compound is an irreversible inhibitor, forming a covalent bond with Cys797 in the EGFR kinase domain. This mechanism allows it to overcome T790M-mediated resistance.
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| ln Vitro |
Olafertinib is a potent inhibitor of mutant EGFR with GI50 values of 5 nM for EGFR L858R/T790M, 10 nM for EGFR del19, and 689 nM for EGFR wild-type. This demonstrates its high selectivity for mutant over wild-type EGFR. The compound inhibits the growth of NSCLC cells harboring EGFR mutations. It is an irreversible inhibitor, forming a covalent bond with the EGFR kinase domain.
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| ln Vivo |
In vivo, olafertinib has been studied in animal models of NSCLC. As an orally bioavailable compound, it demonstrates efficacy in inhibiting tumor growth in xenograft models of EGFR-mutant NSCLC. The compound's ability to overcome T790M-mediated resistance has been demonstrated in preclinical studies.
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| Enzyme Assay |
In vitro assays for olafertinib involve measuring its inhibition of EGFR kinase activity. The kinase is incubated with ATP and a peptide substrate in the presence of varying concentrations of olafertinib. Phosphorylation of the substrate is measured using a luminescent or fluorescent readout. IC50 values are calculated from inhibition curves. Selectivity is assessed by testing the compound against a panel of kinases.
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| Cell Assay |
Cellular assays for olafertinib are performed using NSCLC cell lines harboring EGFR mutations (e.g., H1975 with L858R/T790M, PC-9 with del19). Cells are treated with olafertinib at varying concentrations for 72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. GI50 values are determined from dose-response curves. EGFR phosphorylation and downstream signaling are measured by Western blotting.
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| Animal Protocol |
In vivo animal studies with olafertinib are conducted in mouse xenograft models of NSCLC. Mice bearing subcutaneous tumors of EGFR-mutant NSCLC cells are treated with olafertinib orally at various doses. Tumor volume is measured over time, and tumor growth inhibition is calculated. Pharmacodynamic markers, such as EGFR phosphorylation, are assessed in tumor tissue.
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| ADME/Pharmacokinetics |
Olafertinib is orally bioavailable. Its molecular weight is 512.56 g/mol, and its molecular formula is C29H28F2N6O2. The compound is metabolized in the liver, and its half-life supports once-daily dosing. For research use, it is typically dissolved in DMSO for in vitro studies and formulated in suitable vehicles for oral administration.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for olafertinib are limited. As an EGFR inhibitor, it may cause adverse effects including skin rash, diarrhea, and hepatotoxicity. No significant toxicity has been reported in preclinical studies at therapeutic doses. The compound is intended for research use and should be handled with standard safety precautions.
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| References |
Description: Olafertinib, formerly known as CK-101 and Olafertinib, is a potent and orally bioavailable EGFR mutant-specific inhibitor. CK-101 specifically and covalently binds to and inhibits specific EGFR mutations, with particularly high selectivity against the T790M mutation; this prevents EGFR mutant-mediated signaling and leads to cell death in EGFR mutant-expressing tumor cells. Compared to some other EGFR inhibitors, CK-101 may have therapeutic benefits in tumors with T790M-mediated drug resistance. |
| Additional Infomation |
CK-101, an EGFR mutation-specific inhibitor, is an orally administered third-generation selective EGFR inhibitor that inhibits certain activating mutations of the epidermal growth factor receptor (EGFR), including resistance mutations T790M, L858R, and del 19, and possesses potential antitumor activity. After administration, CK-101 specifically covalently binds to and inhibits specific EGFR mutations, exhibiting particularly high selectivity for the T790M mutation, thereby blocking EGFR mutation-mediated signaling and ultimately leading to the death of tumor cells expressing EGFR mutations. Compared to some other EGFR inhibitors, CK-101 may offer a therapeutic advantage against T790M-mediated resistant tumors. This drug exhibits very low activity against wild-type EGFR (WT EGFR) and does not cause the dose-limiting toxicities associated with the use of non-selective EGFR inhibitors (which also inhibit WT EGFR). EGFR is a receptor tyrosine kinase that is mutated in various tumor cell types and plays a crucial role in tumor cell proliferation and tumor angiogenesis.
Olafertinib is a third-generation EGFR TKI developed for the treatment of NSCLC with EGFR mutations, including the T790M resistance mutation. It is an irreversible inhibitor with high selectivity for mutant EGFR over wild-type EGFR. The compound has been studied in preclinical models and has shown promise in overcoming T790M-mediated resistance. Olafertinib is not approved for clinical use and is intended for laboratory research only. |
| Molecular Formula |
C29H28F2N6O2
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|---|---|
| Molecular Weight |
530.5798
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| Exact Mass |
530.224
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| CAS # |
1660963-42-7
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| Related CAS # |
1660963-42-7;
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| PubChem CID |
117909640
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.674
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| LogP |
4.14
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
815
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IDRGFNPZDVBSSE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H28F2N6O2/c1-2-25(39)33-21-7-3-5-19(17-21)22-8-4-6-20-18-32-29(35-28(20)22)34-23-9-10-24(27(31)26(23)30)37-13-11-36(12-14-37)15-16-38/h2-10,17-18,38H,1,11-16H2,(H,33,39)(H,32,34,35)
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| Chemical Name |
N-[3-[2-[2,3-difluoro-4-[4-(2-hydroxyethyl)piperazin-1-yl]anilino]quinazolin-8-yl]phenyl]prop-2-enamide
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| Synonyms |
CK-101 CK 101 CK101 RX-518 RX 518 RX518 Olafertinib
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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) |
DMSO : ~125 mg/mL (~235.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.92 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 20.8 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 (3.92 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 | 1.8847 mL | 9.4236 mL | 18.8473 mL | |
| 5 mM | 0.3769 mL | 1.8847 mL | 3.7695 mL | |
| 10 mM | 0.1885 mL | 0.9424 mL | 1.8847 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.
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