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Nazartinib

Catalog No. T3506 CAS 1508250-71-2

Synonyms: EGF816, NVS-816

Nazartinib (EGF816) (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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Nazartinib, CAS 1508250-71-2

Pack Size	Availability	Price/USD
1 mg	In stock	$ 31.00
5 mg	In stock	$ 72.00
10 mg	In stock	$ 122.00
25 mg	In stock	$ 197.00
50 mg	In stock	$ 372.00
100 mg	In stock	$ 556.00
500 mg	In stock	$ 1,220.00
1 mL * 10 mM (in DMSO)	In stock	$ 79.00

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Purity: 98.63%

Purity: 98%

Biological Description

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Storage & Solubility Information

Description	Nazartinib (EGF816) (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.
Targets&IC50	EGFR (mutant):0.031 μM(Ki)
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. 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.
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. 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 Clinicalal trials in patients harboring EGFR mutations, including T790M.
Kinase Assay	Recombinant kinase domain of EGFR L858R and T790M-L858R mutants are incubated with EGF816 to confirm covalent modification of EGFR and site of adduction. Recombinant enzyme is incubated at room temperature with a 20-fold molar excess of compound in 40 mM Tris, pH 8, 500 mM NaCl, 1% glycerol, 5 mM TCEP for 1 h. The reaction is quenched by addition of dithiothreitol (DTT, 80-fold excess to compound) and transfer to ice. A third of the reaction (10 μL) is processed for intact MS by adding an equal volume of 6 M Guan HCl, 100 mM Tris, pH 8, 20 mM DTT, 10 mM TCEP and incubating at room temperature for 15 min. Intact MS analysis is performed on an Agilent 6520 QToF mass spectrometer equipped with a dual spray ion source (IS of 4500 V, fragmentor of 250 V, fas temp of 350°C, and skimmer of 75 V). The samples are injected onto a PLRP-S column (2.1 mm × 50 mm), heated to 60°C, and desalted for 2 min at 500 μL/min and 3% B prior to elution with a fast gradient of 3-50% B in 3 min (B, 0.1% formic acid). The data are analyzed in MassHunter for automatic peak selection, integration, and spectral deconvolution with a mass range of 15?000-75?000 Da.
Cell Research	H1975, H3255, HCC827, A431, and HaCaT cells are maintained in RPMI media supplemented with antibiotics and 10% FBS, maintained in a 37°C, 5% CO2 humidified incubator. After an overnight incubation in 384-well plates, serial diluted compounds are transferred to cells and incubated for 3 hours. HaCaT cells are stimulated with 10 ng/mL EGF (50 ng/mL EGF for A431) for 5 minutes. Cells are lysed in 1% Triton X-100 buffer containing protease and phosphatase inhibitors. Lysates are analyzed by sandwich ELISA utilizing goat anti-EGFR capture antibody, anti-phospho-EGFR(Y1173), and anti-rabbit HRP. Signal is measured by chemiluminescent detection.(Only for Reference)

Synonyms	EGF816, NVS-816
Molecular Weight	495.02
Formula	C26H31ClN6O2
CAS No.	1508250-71-2

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: 92 mg/mL (185.9 mM)

DMSO: 92 mg/mL (185.9 mM)

H2O: < 1 mg/mL (insoluble or slightly soluble)

References and Literature

1. Gérald Lelais, et al. J Med Chem. 2016, 59(14), pp 6671-6689 2. Jia Y, et al. Cancer Res. 2016, 76(6):1591-602.

Related compound libraries

This product is contained In the following compound libraries：

Kinase Inhibitor Library Anti-Cancer Drug Library Anti-Cancer Active Compound Library Highly Selective Inhibitor Library Anti-Cancer Clinical Compound Library Inhibitor Library Tyrosine Kinase Inhibitor Library Drug Repurposing Compound Library NO PAINS Compound Library Anti-Prostate Cancer Compound Library

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Keywords

Nazartinib 1508250-71-2 Angiogenesis JAK/STAT signaling Tyrosine Kinase/Adaptors EGFR NVS 816 inhibit HER1 Epidermal growth factor receptor NVS816 EGF 816 ErbB-1 Inhibitor EGF816 EGF-816 NVS-816 inhibitor

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