CP-724714

CP-724714 is An orally bioavailable quinazoline with potential antineoplastic activity. CP-724,714 selectively binds to the intracellular domain of HER2, reversibly inhibiting its tyrosine kinase activity and resulting in suppression of tumor cell growth. HER2, a member of the epidermal growth factor receptor (EGFR) family, is overexpressed in many adenocarcinomas, particularly breast cancers.

Product information

CAS Number: 383432-38-0

Molecular Weight: 469.53

Formula: C27H27N5O3

Synonym:

CP 724714

CP724714

CP-724714 (E-Double bond)

Chemical Name: 2-methoxy-N-[(2E)-3-[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-6-yl]prop-2-en-1-yl]acetamide

Smiles: COCC(=O)NC/C=C/C1C=CC2=NC=NC(NC3C=C(C)C(=CC=3)OC3=CC=C(C)N=C3)=C2C=1

InChiKey: LLVZBTWPGQVVLW-SNAWJCMRSA-N

InChi: InChI=1S/C27H27N5O3/c1-18-13-21(8-11-25(18)35-22-9-6-19(2)29-15-22)32-27-23-14-20(7-10-24(23)30-17-31-27)5-4-12-28-26(33)16-34-3/h4-11,13-15,17H,12,16H2,1-3H3,(H,28,33)(H,30,31,32)/b5-4+

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: DMSO : ≥ 50 mg/mL (106.49 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: ≥360 days 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:

CP-724714 is >1, 000-fold less potent for insulin receptor, insulin-like growth factor-I receptor, platelet-derived growth factor β, vascular endothelial growth factor 2, Abl, Src, c-Met, JNK-2, JNK-3, ZAP-70, Cdk-2, and Cdk-5. CP-724714 potently reduces the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain at a concentration as low as 50 nmol/L (IC50=32 nM) but is markedly less potent against EGFR. CP-724714 (1 μM; 24 hours) induces G1 cell cycle block in vitro in erbB2-overexpressing BT-474 human breast carcinoma cells.

In Vivo:

CP-724714 (3.25-100 mg/kg; p.o.; 0.5-8 hours) results in a concentration-dependent reduction of ErbB2 receptor phosphorylation. CP-724714 (6.25-100 mg/kg; p.o.; q.d; for 8 to 40 day) inhibits FRE-erbB2 xenograft growth. CP-724714 (Athymic, female FRE-erbB2 xenograft-bearing mice; 30 or 100 mg/kg; p.o.) treatments results in a time- and dose- dependent induction of apoptosis, which was evident as early as 4 to 8 h after dosing. Approximately 75% more tumor cells exhibited apoptotic changes in the 100 mg/kg treatment group compared with vehicle control group at 8 h after dosing. CP-724714 induces regression of BT-474 tumors and significant inhibition in a number of other human tumor xenografts. Additionally, CP-724714 showed a favorable nonclinical toxicity profile with no apparent effects on cardiac tissue.

References:

1. Feng B, et al. Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714. Toxicol Sci, 2009, 108(2), 492-500.
2. Jani JP, et al. Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor. Cancer Res, 2007, 67(20), 9887-9893.

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