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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Nazartinib mesylate (formerly known as EGF816 mesylate and NVS-816 mesylate) is a novel, covalent/irreversible, and mutant-selective EGFR inhibitor with Ki and Kinact of 31 nM and 0.222 min−1 on EGFR(L858R/790M) mutant, respectively. Nazartinib specifically targets EGFR-activating mutations arising de novo and upon resistance acquisition, while sparing wild-type (WT) EGFR. Non-small cell lung cancer patients carrying oncogenic EGFR mutations initially respond to EGFR-targeted therapy, but later elicit minimal response due to dose-limiting toxicities and acquired resistance.Nazartinib potently inhibits the most common EGFR mutations L858R, Ex19del, and T790M in vitro. The cellular activity of EGF816 on EGFR mutants are assessed using three well-characterized cell lines, H3255, HCC827, and H1975, which harbor the L858R, Ex19del, and L858R/T790M mutations, respectively. Nazartinib is currently under clinical evaluation (phase I/II clinical trials) in patients harboring EGFR mutations, including T790M.
| ln Vitro |
Nazartinib (EGF816) exhibits enhanced ADME and PK characteristics and exhibits an inhibitory effect on the mutant cell lines H1975, H3255, and HCC827, with IC50s of 4, 6, and 2 nM, respectively[1]. In H3255, HCC827, and H1975 cell lines, napardinib (EGF816) exhibits strong suppression of pEGFR levels with EC50 values of 5, 1, and 3 nM, respectively. On HCC827 and H1975, napartinib's OC50 (compound concentration at 50% occupancy) values are 2 and 5 nM, respectively[2].
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| ln Vivo |
Nazartinib (EGF816; 50 and 20 mg/kg or 25 mg/kg, po) exhibits dose-dependent effectiveness in the H1975 mouse xenograft model, with nearly total tumor cell regression at the highest dose examined (50 mg/kg)[1]. Nazartinib (EGF816; 10 mg/kg, po) in the H1975 mouse model causes tumor growth inhibition with a T/C (tumor/control volume) of 29%. Tumor regressions are attained at dosages of 30 and 100 mg/kg (T/C, −61% and −80%, respectively). Significant anticancer efficacy is demonstrated by naparsetinib (30 mg/kg, po) in the H3255 xenograft model. Nazartinib selectively inhibits cell lines having EGFR with catalytic domain mutations, as evidenced by its antiproliferative efficacy on 89 lung cancer cell lines[2].
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| References |
[1]. Lelais G, et al. Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T79
[2]. Jia Y, et al. EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor. Cancer Res. 2016 Mar 15;76(6):1591-602 |
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| Additional Infomation |
See also: Nazartinib Mesylate (annotation moved to).
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| Molecular Formula |
C₂₇H₃₅CLN₆O₅S
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|---|---|---|
| Molecular Weight |
591.12
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| Exact Mass |
590.207
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| CAS # |
1508250-72-3
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| Related CAS # |
Nazartinib;1508250-71-2;Nazartinib S-enantiomer;1508256-20-9
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| PubChem CID |
91809207
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
40
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| Complexity |
857
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C(C1=CC(C)=NC=C1)NC2=NC3=CC=CC(Cl)=C3N2[C@H]4CN(C(/C=C/CN(C)C)=O)CCCC4.CS(=O)(O)=O
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| InChi Key |
BJRYTAMUVASSBY-ZJULCNDBSA-N
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| InChi Code |
InChI=1S/C26H31ClN6O2.CH4O3S/c1-18-16-19(12-13-28-18)25(35)30-26-29-22-10-6-9-21(27)24(22)33(26)20-8-4-5-15-32(17-20)23(34)11-7-14-31(2)3;1-5(2,3)4/h6-7,9-13,16,20H,4-5,8,14-15,17H2,1-3H3,(H,29,30,35);1H3,(H,2,3,4)/b11-7+;/t20-;/m1./s1
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| Chemical Name |
N-[7-chloro-1-[(3R)-1-[(E)-4-(dimethylamino)but-2-enoyl]azepan-3-yl]benzimidazol-2-yl]-2-methylpyridine-4-carboxamide;methanesulfonic acid
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6917 mL | 8.4585 mL | 16.9170 mL | |
| 5 mM | 0.3383 mL | 1.6917 mL | 3.3834 mL | |
| 10 mM | 0.1692 mL | 0.8459 mL | 1.6917 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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