Nazartinib

SKU: orb1304136

Description

Nazartinib (EGF816) is an irreversible, mutant-selective EGFR inhibitor. It potently and selectively targets common activating mutations (L858R, ex19del) and the T790M resistance mutation, showing significant selectivity over wild-type EGFR in biochemical and cellular assays. Its research applications include in vitro mechanistic studies and in vivo models of non-small cell lung cancer (NSCLC).

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1508250-71-2
• MW: 495.02
• Purity: 99.62% (May vary between batches)
• Formula: C₂₆H₃₁ClN₆O₂
• SMILES: CN(C)C\C=C\C(=O)N1CCCC[C@H](C1)n1c(NC(=O)c2ccnc(C)c2)nc2cccc(Cl)c12
• Target: EGFR
• Solubility: Ethanol:92 mg/mL (185.85 mM);DMSO:92 mg/mL (185.85 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  EGFR (mutant):0.031 μM(Ki)
• In Vivo:
  Nazartinib 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, Nazartinib shows high clearance and high volume of distribution. Nazartinib also demonstrates antitumor activity in an exon 20 insertion mutant model. At levels above efficacious doses, Nazartinib treatment leads to minimal inhibition of WT EGFR and is well tolerated. In single-dose studies, Nazartinib provides sustained inhibition of EGFR phosphorylation, consistent with its ability for irreversible binding. Nazartinib 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.
• In Vitro:
  Nazartinib 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. Nazartinib potently inhibits the most common EGFR mutations L858R, Ex19del, and T790M in vitro. The cellular activity of Nazartinib 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, Nazartinib 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 Nazartinib is selective toward mutant over WT EGFR.
• 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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

EGF 816, EGFR, EGF-816, EGF816, EGFR (mutant), Epidermal growth factor receptor, ErbB-1, HER1, Inhibitor, inhibit, Nazartinib, NVS 816, NVS816, NVS-816

Compound Identifiers

PubChem CID

72703790