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Formula | C26H31ClN6O2 |
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Molecular Weight | 495.02 | CAS No. | 1508250-71-2 | |
Solubility (25°C)* | In vitro | DMSO | 99 mg/mL (199.99 mM) | |
Ethanol | 99 mg/mL (199.99 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Nazartinib (EGF816, NVS-816) is a covalent, irreversible, mutant-selective EGFR inhibitor that has nanomolar inhibitory potency against activating mt (L858R, ex19del) and T790M mt, with up to 60-fold selectivity over wild type (wt) EGFR in vitro. | ||
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In vitro | EGF816 is a novel, covalent, mutant-selective EGFR inhibitor with nearly equipotent activity on both oncogenic (L858R and ex19del) and T790M-resistant mutations and good selectivity over WT EGFR[1]. EGF816 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. After incubation with cells for 3 hours, EGF816 shows potent inhibition of pEGFR levels in H3255, HCC827, and H1975 with EC50 values of 5, 1, and 3 nmol/L, respectively. Cellular-based assays shows that EGF816 is selective toward mutant over WT EGFR[2]. | ||
In vivo | EGF816 is well tolerated and possesses favorable physicochemical properties and good oral bioavailability in mice. It shows moderate volume of distribution and low to moderate clearance in rodents (30% and 35% of rat and mouse liver blood flow, respectively). In the dog, EGF816 shows high clearance and high volume of distribution[1]. EGF816 also demonstrates antitumor activity in an exon 20 insertion mutant model. At levels above efficacious doses, EGF816 treatment leads to minimal inhibition of WT EGFR and is well tolerated. In single-dose studies, EGF816 provides sustained inhibition of EGFR phosphorylation, consistent with its ability for irreversible binding. EGF816 has a longer half-life in human than mouse and is currently being evaluated in phase I/II clinical trials in patients harboring EGFR mutations, including T790M[2]. |
Cell Assay:[2] |
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Animal Study:[1] |
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Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity [ Cancer Cell, 2022, 40(7):754-767.e6] | PubMed: 35820397 |
IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells [ Sci Signal, 2022, 15(747):eabj5879] | PubMed: 35973030 |
Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity. [ Cancer Cell, 2019, 10.1016/j.ccell.2019.09.001] | PubMed: 31588020 |
Preclinical Modeling of Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutations. [ J Thorac Oncol, 2019, 14(9):1556-1566] | PubMed: 31108249 |
The Third-Generation EGFR Inhibitor, Osimertinib, Promotes c-FLIP Degradation, Enhancing Apoptosis Including TRAIL-Induced Apoptosis in NSCLC Cells with Activating EGFR Mutations [ Transl Oncol, 2019, 12(5):705-713] | PubMed: 30856555 |
Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. [ Nat Med, 2018, 24(5):638-646] | PubMed: 29686424 |
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.