Osimertinib

SKU: orb1305406

Description

Osimertinib (AZD-9291) is an oral, irreversible third-generation EGFR inhibitor designed to target the T790M resistance mutation in non-small cell lung cancer (NSCLC). It is widely used in preclinical research, demonstrating potent antitumor activity in both in vitro cell assays and in vivo xenograft models of EGFR-mutant NSCLC.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1421373-65-0
• MW: 499.61
• Purity: 100.00%
• Formula: C₂₈H₃₃N₇O₂
• SMILES: CN1C=C(C=2C1=CC=CC2)C3=NC(NC4=C(OC)C=C(N(CCN(C)C)C)C(NC(C=C)=O)=C4)=NC=C3
• Target: EGFR
• Solubility: DMSO:120 mg/mL (240.19 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:9.2 mg/mL (18.41 mM);Ethanol:22 mg/mL (44.03 mM)

Bioactivity

• Target IC50:
  MNK2:48.6 nM|EGFR (WT):493.8 nM|MNK1:324 nM|H1975 cells:1.78 μM|PC9 cells:0.66 μM|EGFR (exon 19 deletion):12.92 nM|EGFR (L858R/T790M):11.44 nM
• In Vivo:
  In mutant EGFR cell lines, AZD9291 effectively inhibits cell proliferation.
• In Vitro:
  In the EGFRm+ (PC9) and EGFRm+/T790M (H1975) tumor models, oral administration of AZD9291 (5 mg/kg) effectively inhibits AKT and ERK signaling pathways as well as EGFR phosphorylation in tumors, leading to tumor regression.
• Cell Research:
  AZD-9291 is dissolved in DMSO and stored, and then diluted with appropriate medium before use. PC-9 cells are seeded into T75 flasks (5×105 cells/flask) in RPMI growth media and incubated at 37°C, 5% CO2. The following day the media is replaced with media supplemented with a concentration of EGFR inhibitor equal to the EC50 concentration predetermined in PC-9 cells. Media changes are carried out every 2-3 days and resistant clones allowed to grow to 80% confluency prior to the cells being trypsinised and reseeded at the original seeding density in media containing twice the concentration of EGFR inhibitor. Dose escalations are continued until a final concentration of 1.5 μM Gefitinib, 1.5 μM Afatinib, 1.5 μM WZ4002 or 160 nM AZD-9291 are achieved.

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

PC-9, Osimertinib, Inhibitor, inhibit, Mereletinib, HER1, H1975, EGFR, EGFR (Exon 19 deletion), EGFR (L858R/T790M), Epidermal growth factor receptor, ErbB-1, AZD 9291, AZD9291, AZD-9291, Ba/F3 cells, cancer, tumor xenograft model

Compound Identifiers

PubChem CID

71496458