Physicochemical Properties
| Molecular Formula | C27H27N5O3 |
| Molecular Weight | 469.53 |
| Exact Mass | 469.211 |
| CAS # | 383432-38-0 |
| Related CAS # | (E/Z)-CP-724714;537705-08-1 |
| PubChem CID | 9874913 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 687.3±55.0 °C at 760 mmHg |
| Flash Point | 369.5±31.5 °C |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.663 |
| LogP | 4.05 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 35 |
| Complexity | 692 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CC1=NC=C(C=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3C=C(C=C4)/C=C/CNC(=O)COC)C |
| InChi Key | LLVZBTWPGQVVLW-SNAWJCMRSA-N |
| InChi Code | 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+ |
| Chemical Name | 2-methoxy-N-[(E)-3-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-6-yl]prop-2-enyl]acetamide |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | ErbB2 10 nM (IC50) |
| ln Vitro | 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 are among the receptors for which CP-724714 is >1,000 times less potent[1]. At concentrations as low as 50 nmol/L (IC50=32 nM), CP-724714 potently inhibits the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain; however, its potency against EGFR is noticeably lower[1]. In vitro, CP-724714 (1 μM; 24 hours) causes G1 cell cycle block in BT-474 human breast carcinoma cells that overexpress erbB2[1]. |
| ln Vivo | ErbB2 receptor phosphorylation is reduced in a concentration-dependent manner by CP-724714 (3.25-100 mg/kg; po; 0.5-8 hours)[1]. CP-724714 (6.25–100 mg/kg; po; qd; for 8–40 days) suppresses the growth of FRE-erbB2 xenografts[1]. Apoptosis is induced in response to CP-724714 (Athymic, female FRE-erbB2 xenograft-bearing mice; 30 or 100 mg/kg; po) in a time- and dose-dependent manner. This was seen as early as 4 to 8 hours following dosing. Eight hours after dose, over 75% more tumor cells in the 100 mg/kg treatment group showed signs of apoptosis than in the vehicle control group. Regression of BT-474 tumors and considerable suppression of several other human tumor xenografts are induced by CP-724714. Furthermore, CP-724714 had no discernible effects on heart tissue and a positive nonclinical toxicity profile[1]. |
| Cell Assay |
Cell Cycle Analysis[1] Cell Types: erbB2-amplified BT-474 breast cancer cells Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Resulted in accumulation of cells in G1 phase and a marked reduction in S-phase cells. |
| Animal Protocol |
Animal/Disease Models: Female athymic mice (bearing FRE-erbB2 xenografts)[1] Doses: 3.25-100 mg/kg Route of Administration: Po; 0.5-8 hrs (hours) Experimental Results: Produced a reduction of erbB2 tyrosine phosphorylation in FRE-erbB2 xenografts. Animal/Disease Models: Athymic female mice bearing FRE-erbB2 xenografts[1] Doses: 6.25- 100 mg/kg Route of Administration: Po; qd; for 8 to 40 day Experimental Results: Resulted in an inhibition of FRE-erbB2 xenografts. |
| References |
[1]. Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor. Cancer Res, 2007, 67(20), 9887-9893. [2]. 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. |
| Additional Infomation |
CP-724714 is a 2-methoxy-N-[3-[4-[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]anilino]-6-quinazolinyl]prop-2-enyl]acetamide in which the double bond adopts a trans-configuration. It is a potent inhibitor of HER2/ErbB2 (IC50 = 10 nM) and exhibits anti-cancer activity. It has a role as an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, an antineoplastic agent, an apoptosis inducer and a hepatotoxic agent. CP-724,714 has been used in trials studying the treatment of Breast Cancer, Breast Neoplasms, and Neoplasm Metastasis. HER2 Inhibitor CP-724,714 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. (NCI04) |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 50 mg/mL (106.49 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1298 mL | 10.6489 mL | 21.2979 mL | |
| 5 mM | 0.4260 mL | 2.1298 mL | 4.2596 mL | |
| 10 mM | 0.2130 mL | 1.0649 mL | 2.1298 mL |