Canertinib

Canertinib (CI-1033;PD-183805) is a potent and irreversible EGFR inhibitor; inhibits cellular EGFR and ErbB2 autophosphorylation with IC50s of 7.4 and 9 nM.

Product information

CAS Number: 267243-28-7

Molecular Weight: 485.94

Formula: C24H25ClFN5O3

Synonym:

CI1033

CI 1033

CI-1033

PD183805

PD 183805

PD-183805

Canertinib free base

Related CAS Number:

289499-45-2 (Canertinib HCl)

Chemical Name: N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)propoxy]quinazolin-6-yl}prop-2-enamide

Smiles: C=CC(=O)NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1OCCCN1CCOCC1

InChiKey: OMZCMEYTWSXEPZ-UHFFFAOYSA-N

InChi: InChI=1S/C24H25ClFN5O3/c1-2-23(32)30-21-13-17-20(14-22(21)34-9-3-6-31-7-10-33-11-8-31)27-15-28-24(17)29-16-4-5-19(26)18(25)12-16/h2,4-5,12-15H,1,3,6-11H2,(H,30,32)(H,27,28,29)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 2 mg/mL(4.11 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

In Vivo:

CI-1033 shows impressive activity against A431 xenografts in nude mice at 5 mg/kg of body weight. CI-1033 (20 to 80 mg/kg/d) achieves a high degree of tumor regressions in H125 xenograft models. Oral administration of CI-1033 causes a marked inhibition of growth in TT, TE6 and TE10 xenografts in nude mice, without animal death and <10% weight loss.

References:

1. Smaill JB et al. J Med Chem. 2000; 43(7): 1380-1397.
2. Nelson JM et al. J Biol Chem. 2001; 276(18): 14842-14827.
3. Slichenmyer WJ et al. Semin Oncol. 2001; 28(5 Suppl 16): 80-85.
4. Citri A et al. EMBO J. 2002; 21(10): 2407-2417.
5. Hughes DP et al. Pediatr Blood Cancer. 2006; 46(5): 614-623.
6. Ako E et al. Oncol Rep. 2007; 17(4): 887-893.
7. Erlichman C, et al. Cancer Res, 2001, 61(2), 739-748.

Products are for research use only. Not for human use.