AZD-9291

SKU: orb1226317

Description

A potent, selective, third-generation irreversible inhibitor of mutant EGFR with IC50s of 1/12/5 nM for L858R-T790M/L858R/L861Q respectively; weak activity against wt EGFR (IC50=184 nM); inhibits signaling pathways and cellular growth in both EGFRm(+) and EGFRm(+)/T790M(+) mutant cell lines in vitro; exhibits tumor regression in EGFR-mutant tumor xenograft and transgenic models; orally active.Lung Cancer Approved(In Vitro):Osimertinib (AZD9291) (0-10 μM; 72 hours) dramatically inhibits cell proliferation with IC50s of 41, 26, 41, and 31 nM, respectively.Osimertinib (0-10 μM; 72 hours) inhibits cell proliferation (Ba/F3 cells harboring a T790M mutation, exon 19del+T790M, or L858R+T790M) with IC50s of 6, 7, and 74 nM, respectively.Osimertinib (0-10 μM; 72 hours) inhibits Ba/F3 cells harboring EGFR exon 20 insertion mutations (IC50 ranging from 16 to 701 nM for A763_Y764insFQEA (FQEA), Y764_V765insHH (HH), A767_V769dupASV (ASV), and D770_N771insNPG (NPG) cells).Osimertinib shows high levels of phenotype potency in both sensitizing-mutant (mean IC50 of 8 nM in PC-9) and T790M (mean IC50s of 11 and 40 nM in H1975 and PC-9VanR respectively) EGFR cell lines. Osimertinib has much less activity towards wild-type EGFR (mean IC50s of 650 and 461 nM in Calu3 and H2073 respectively).Osimertinib (0.1 μM; 48 hours) induces apoptosis in Ba/F3 cells (apoptosis rates of 40.9% and 90% in EGFR exon 19del+T790M, EGFR L858R+T790M respectively) (In Vivo):Osimertinib (0.1-25 mg/kg; p.o.; daily for 14 days) induces significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models.

Key Properties

• CAS Number: 1421373-65-0
• MW: 499.6073
• Purity: >98% (HPLC)
• Formula: C₂₈H₃₃N₇O₂
• SMILES: COC1=C(NC2=NC=CC(=N2)C2=CN(C)C3=CC=CC=C23)C=C(NC(=O)C=C)C(=C1)N(C)CCN(C)C
• Target: EGFR
• Solubility: DMSO: ≥ 30 mg/mL

Bioactivity

• In Vivo:
  Animal model: PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models. Dosage: 0.1-10 mg/kg (PC-9 xenograft models); 0.5-25 mg/kg (H1975 xenograft models). Administration: p.o. ; daily for 14 days. Result: Induced significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models.
• In Vitro:
  Cell Proliferation Assay Cell line: Ba/F3 cells (harboring a T790M mutation, exon 19del+T790M, or L858R+T790M). Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation time: 72 hours. Result: Inhibited cell proliferation (IC50s=6, 7, 74 nM, respectively)Cell Proliferation Assay Cell line: PC-9, H3255, PC-9ER, and H1975 cells. Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation time: 72 hours. Result: Dramatically inhibited cell proliferation (IC50s=41, 26, 41, 31 nM, respectively)Cell Proliferation Assay Cell line: Ba/F3 cells (harboring EGFR exon 20 insertion mutations: FQEA, HH, ASV, NPG ). Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM Incubation time: 72 hours. Result: Inhibited cell proliferation (IC50s=16, 701, 230, 38 nM, respectively)Apoptosis Analysis Cell line: Ba/F3 cells (harboring EGFR exon 19del+T790M or EGFR L858R+T790M). Concentration: 0.1 μM Incubation time: 48 hours. Result: Induced apoptosis with the rates of 40.9% and 90% in EGFR T790M positive mutations cells, respectively.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Osimertinib | Mereletinib | AZD9291 | AZD 9291

Quick Database Links

Gene Symbol

EGFR