CP-724714

Pfizer CP-724714, also identified as PF-04733097, is a quinazoline-based, orally active tyrosine kinase inhibitor with marked selectivity for ErbB2/HER2. The CP-724714 molecular structure contains a quinazoline core with substituted aromatic and amide-containing side chains characteristic of ATP-competitive kinase inhibitors. CP-724714 has a molecular weight of 469.21 g/mol and a calculated cLogP of 4.79. This research compound is supplied at 95% purity, with purity validated by NMR and/or LCMS methods, under an agreement with Pfizer Inc.

Application of CP-724714 

Unlike dual EGFR/HER2 inhibitors such as lapatinib, CP-724714 blocks HER2 with roughly 640-fold selectivity over EGFR, which makes it useful for distinguishing HER2-dependent signaling from EGFR-related effects under appropriately controlled assay conditions.  This selectivity profile is particularly relevant in HER2-amplified breast cancer research, where distinguishing receptor-specific contributions to proliferation and survival is important for target-validation studies.  Because the compound advanced into Phase I clinical trials before development was discontinued over hepatotoxicity findings, it also serves researchers studying HER2 inhibitor tolerability and hepatic transporter interactions, alongside its more common use as a target-validation tool in trastuzumab-resistance models.

In Vitro

CP-724714 inhibits ErbB2 kinase activity with an IC50 of 10 nM, compared with roughly 6400 nM against EGFR, and shows more than 1000-fold selectivity over IR, IGF1R, PDGFRβ, VEGFR2, Abl, Src, c-Met, JNK, CDK2 and CDK5 in cell-free assays. In HER2-overexpressing BT-474 breast carcinoma cells, it blocks ErbB2 receptor autophosphorylation and drives a G1 cell cycle arrest with a corresponding drop in S-phase cells.

In Vivo

Oral dosing in athymic mice bearing HER2-driven FRE tumors produced dose-dependent inhibition of ErbB2 autophosphorylation, with an ED50 near 19 mg/kg. In the HER2-amplified BT-474 and MDA-MB-453 xenograft models, CP-724714 treatment slowed tumor growth in a dose-dependent manner and increased tumor cell apoptosis, alongside measurable reductions in downstream ErbB2 signaling.

Biochemical and Physiological Actions

The CP-724714 chemical structure supports ATP-competitive binding at the HER2 kinase domain, where the compound prevents autophosphorylation of the receptor's intracellular tyrosine residues. Because HER2 has no known ligand and signals mainly through heterodimerization with other ErbB family members, blocking its autophosphorylation directly interrupts downstream proliferative signaling in HER2-amplified cells, while producing less direct inhibition of other ErbB-family kinases than broader pan-HER inhibitors at comparable experimental concentrations.

The CP-724714 structure provides a useful reference for mechanistic studies of HER2-selective kinase inhibition.

Features and Benefits of CP-724714

For laboratories studying HER2-driven signaling, CP-724714 offers:

• ATP-competitive, HER2-selective inhibition with minimal cross-reactivity against EGFR and other kinases;
• CAS 383432-38-0 at 95% purity with NMR/LCMS-verified quality control, supplied under agreement from Pfizer Inc.;
• documented in vitro and in vivo activity in HER2-amplified breast cancer models, useful for target-validation and resistance studies;
• reported CP-724714 molecular weight, supporting compound characterization and analytical reference workflows.