Neratinib

SKU: orb1224203

Description

A potent, highly selective, irreversible HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM in cell-free assays; weakly inhibits KDR and Src (IC50=0.8 and 1.4 uM), no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met; inhibits downstream signal transduction events and cell cycle regulatory pathways, leads to arrest at the G(1)-S phase transition, decreases cell proliferation; active in HER-2- and EGFR-dependent tumor xenograft models, orally bioavailable.Breast Cancer Approved.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 698387-09-6
• MW: 557.0427
• Purity: >98% (HPLC)
• Formula: C₃₀H₂₉ClN₆O₃
• SMILES: CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)/C=C/CN(C)C
• Target: EGFR
• Solubility: DMSO: 6.4 mg/mL (Need ultrasonic)

Bioactivity

• In Vivo:
  Animal model: Female athymic (nude) mice, tumor xenograft. Dosage: 10, 20, 40, 60 or 80 mg/kg/day. Administration: Gavage, 42 days. Result: Reduced tumor growth in a dose-dependent manner in 3T3/neu, BT474, SK-OV-3 and A431 xenografts, but was o inactive in xenografts of MX-1 and MCF-7. Inhibited phosphorylation of HER-2 in BT474 xenografts.
• In Vitro:
  Cell Proliferation Assay Cell line: 3T3, 3T3/neu, SK-Br-3, BT 474, A431, MDA-MB-435 and SW620. Concentration: 0.5 ng/mL-5 μg/mL Incubation time: 2 days (6 days for BT474). Result: Inhibited cell proliferation with IC50 values of 700 ± 78, 3 ± 0.14, 2 ± 0.18, 2 ± 0.06, 81± 9, 960 ± 165 and 690 ± 84 nM against 3T3, 3T3/neu, SK-Br-3, BT 474, A431, MDA-MB-435 and SW620 cells, respectively. Western blot analysis. Cell line: BT474 or A431 cells. Concentration: 0, 2, 10, 50, 100 and 200 nM. Incubation time: 3 h. Result: Decreased ligand-independent receptor phosphorylation by 50% (IC50) at 5 nM in BT474 cells, repressed EGF-dependent phosphorylation of EGFR in A431 cells at a comparable dose (IC50 = 3 nM). Effectively repressed phosphorylation of MAPK and Akt in BT474 cells. Cell Cycle Analysis Cell line: BT474. Concentration: 0-2 nM. Incubation time: 12-16 h. Result: Blocked cell cycle progression, causing a G1-S arrest, a 50% decrease in the number of cells in the S (DNA synthesis) phase of the cell cycle was observed at a concentration of 2 nM.

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

HKI-272 | HKI272 | HKI 272

Quick Database Links

Gene Symbol

EGFR