Canertinib dihydrochloride

SKU: orb1225419

Description

A potent, irreversible, orally available pan-ErbB inhibitor for EGFR and ErbB2 with IC50 of 7.5 nM and 9.0 nM in autophosphorylation assay; displays no activity to PDGFR, FGFR, InsR, PKC, and CDK1/2/4; suppresses heregulin-stimulated tyrosine phosphorylation of erbB2, erbB3 and erbB4 with IC50 of 5, 14 and 10 nM, respectively, also inhibits expression of pp62c-fos in response to heregulin; shows high in vivo activity against A431 xenografts.Lung Cancer Discontinued.

Key Properties

• CAS Number: 289499-45-2
• MW: 558.8603
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₇Cl₃FN₅O₃
• SMILES: C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4.Cl.Cl
• Target: EGFR
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Canertinib dihydrochloride (CI-1033 dihydrochloride) shows superior In vivo antitumor activity, giving growth delays in A431 xenografts exceeding 50 days following oral administration. The growth of human malignant melanoma xenografts, RaH3 and RaH5, in nude mice is significantly inhibited by i.p. injections of 40 mg/kg/day canertinib. The anti-proliferative effect on melanoma xenografts is visible already within 4 days of treatment and further increased throughout the treatment period as observed through the differences in tumor volumes, reaching statistical significance within 18 days of treatment.
• In Vitro:
  Canertinib dihydrochloride (CI-1033 dihydrochloride) significantly inhibits growth of cultured melanoma cells, RaH3 and RaH5, in a dose-dependent manner. IC50 is approximately 0.8 μM and by 5 μM both cell lines are completely growth-arrested within 72 h of treatment. Incubation of exponentially growing RaH3 and RaH5 with 1 μM canertinib accumulated the cells in the G1-phase of the cell cycle within 24 h of treatment without induction of apoptosis. 1 μM canertinib inhibits ErbB1-3 receptor phosphorylation with a concomitant decrease of Akt-, Erk1/2- and Stat3 activity in both cell lines. Canertinib dihydrochloride also is a potent activator of exosome secretion.

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

Canertinib | CI-1033 dihydrochloride | PD-183805 dihydrochloride | CI1033 dihydrochloride

Quick Database Links

Gene Symbol

EGFR