Canertinib

SKU: orb1301044

Description

Canertinib

Research Area

Cardiovascular Research, Infectious Disease & Virology, Signal Transduction

Key Properties

• CAS Number: 267243-28-7
• MW: 485.94
• Purity: 99.83%
• Formula: C₂₄H₂₅ClFN₅O₃
• SMILES: Fc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)c(NC(=O)C=C)cc23)cc1Cl
• Target: EGFR,Virus Protease
• Solubility: DMSO:4.86 mg/mL (10 mM)

Bioactivity

• Target IC50:
  ErbB2:9.0 nM|EGFR:1.5 nM
• In Vivo:
  Canertinib shows impressive activity against A431 xenografts in nude mice at 5 mg/kg of body weight. Canertinib (20 to 80 mg/kg/d) achieves a high degree of tumor regressions in H125 xenograft models. Oral administration of Canertinib causes a marked inhibition of growth in TT, TE6 and TE10 xenografts in nude mice, without animal death and <10% weight loss.
• In Vitro:
  CI-1033 shows excellent potency for irreversible inhibition of erbB2 autophosphorylation in MDA-MB 453 cells. CI-1033 also shows high permeability in Caco-2 cells and inhibits secretory transport of vinblastine, which indicates that CI-1033 is a likely inhibitor of the P-gp. CI-1033 alone, significantly suppresses constitutively activated Akt and MAP kinase. In combination with gemcitabine, CI-1033 inhibits Akt and prevents increased levels of MAPK phosphorylation. CI-1033 stimulates p27 expression and p38 phosphorylation in MDA-MB-453 cells. CI-1033 is highly specific to the erbB receptor family and not sensitive to PGFR, FGFR or IR even at 50 μM. CI-1033 shows high levels of inhibition in A431 cells expressing EGFR with IC50 of 7.4 nM. CI-1033 suppresses heregulin-stimulated tyrosine phosphorylation of erbB2, erbB3 and erbB4 with IC50 of 5, 14 and 10 nM, respectively. CI-1033 also inhibits expression of pp62c-fos in response to heregulin. CI-1033 is predicted to modify Cys773 covalently within the ATP binding site of the HER2 kinase and enhances destruction of both mature and immature ErbB-2 molecules. CI-1033 induces a significant decrease in measurable phosphorylation of tyrosine residues 845 and 1068 of EGFR, which are responsible for Src and Ras/MAPK signaling respectively. The corresponding residues of Her-2, tyrosine residues 877 and 1248 are dephosphorylated significantly by CI-1033 at a concentration of 3 μM or higher. CI could block EGFR internalization and increase the rate of apoptosis in primary osteosarcoma cells in a titratable fashion. In addition, CI-1033 inhibits the proliferation of TT, TE2, TE6 and TE10 cells significantly at 0.1 nM.
• Cell Research:
  Cells (1 × 104) are seeded in each well of a 24-well plastic culture plate and left overnight in DMEM or RPMI-1640 supplemented with 10% FBS. The next morning, the cells are treated with the indicated concentrations of CI-1033 (0.1-5.0 nM) for varying periods (1, 3, 5 and 7 days). After treatment, the cells are counted using a Coulter counter. The percent of cell proliferation is calculated by this formula: treatment cell number/control cell number × 100 for each time period.(Only for Reference)

Storage & Handling

• Storage: store under nitrogen,store at low temperature | 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

PD183805, PD-183805, PD 183805, Orthopoxvirus, inhibit, Inhibitor, ErbB-1, Epidermal growth factor receptor, EGFR, HER1, HER2/ErbB2, Canertinib, CI 1033, CI1033, CI-1033

Compound Identifiers

PubChem CID

156414