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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
CP-724714 (CP724714) is an orally bioavailable, potent, selective inhibitor of HER2/ErbB2 with potential anticancer activity. Its IC50 value for HER2/ErbB2 inhibition is 10 nM. In cell-free experiments, CP 724714 exhibits >640-fold selectivity for blocking HER2/ErbB2 over EGFR, InsR, IRG-1R, PDGFR, VEGFR2, Abl, Src, c-Met, etc.
Targets |
HER2/ErbB2 (IC50 = 10 nM)
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ln Vitro |
CP-724,714 exhibits a 6.4 μM IC50 and is specifically marked against EGFR. For IR, IGF-1R, PDGFRβ, VGFR2, abl. Src, c-Met c-jun NH2-terminal kinase (JNK)-2, JNK-3, ZAP-70, cyclin-dependent kinase (CDK)-2, and CDK-5, CP-724,714 is >1,000 times less potent. With an IC50 of 32 nM, CP-724,714 potently inhibits the EGF-induced autophosphorylation of the erbB2 kinase domain chimera, but it is noticeably less effective against EGFR in transfected NIH3T3 cells. With an IC50 of 0.25 and 0.95 μM, CP-724,714 selectively suppresses the growth of erbB2-amplified cells, such as BT-474 and SKBR3. At 1 μM, CP-724,714 causes BT-474 cells to accumulate in the G1 phase and significantly decrease in the S-phase. (Source: ) It is probable that CP-724,714 causes hepatotoxicity through a combination of hepatocellular damage and hepatobiliary cholestatic mechanisms. Cholyl-lysyl fluorescein and taurocholate (TC) efflux into canaliculi in cryopreserved and fresh cultured human hepatocytes, respectively, are both inhibited by CP-724,714. With an IC50 of 16 μM, CP-724,714 inhibits TC transport in membrane vesicles expressing the human bile salt export pump. Additionally, with an IC50 of ~28 μM, it inhibits MDR1, the main efflux transporter in bile canaliculi.[2]
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ln Vivo |
CP-724,714 (25 mg/kg) is rapidly absorbed following intraperitoneal injection and, in FRE-erbB2 or BT-474 xenografts, results in a decrease in tumor erbB2 receptor phosphorylation following dosage. In mice bearing FRE-erbB2 xenografts (s.c.), CP-724,714 causes apoptosis and, at 50 mg/kg, exhibits 50% inhibition of tumor growth without causing weight loss or death. Additionally, in MDA-MB-453, MDA-MB-231, LoVo (colon), and Colo-205 (colon) xenografts, CP-724,714 exhibits strong antitumor activity. Moreover, in BT-474 xenografts, CP-724,714 (30 or 100 mg/kg) lowers Akt phosphorylation and extracellular signal-regulated kinase.[1]
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Enzyme Assay |
Baculovirus-infected Sf9 cells express recombinant erbB2 (amino acid residues 675–1255) and EGFR (amino acid residues 668–1211) intracellular domains as glutathione S-transferase fusion proteins. To be used in the assay, the proteins are purified using affinity chromatography on glutathione Sepharose beads. Not at all MaxiSorp 96-well plates are coated by incubating 100 μL/well of 0.25 mg/mL poly(Glu:Tyr, 4:1), PGT in PBS for an entire night at 37 °C. After aspirating out any excess PGT, the plate is three times cleaned with wash buffer (0.1% Tween 20 in PBS). The kinase reaction takes place in 50 μL of 50 mm HEPES (pH 7.4), which also contains approximately 15 ng of recombinant protein, 125 mm sodium chloride, 10 mm magnesium chloride, 0.1 mm sodium orthovanadate, 1 mm ATP, and magnesium chloride. The final concentration of DMSO is 2.5% after inhibitors are added. When ATP is added, phosphorylation begins and continues for six minutes at room temperature while being constantly shaken. Aspiration of the reaction mixture and four washes with wash buffer are used to stop the kinase reaction. Following a 25-minute incubation with 50 μL/well HRP conjugated-PY54 antiphosphotyrosine antibody, diluted to 0.2 μg/mL in blocking buffer (3% BSA, 0.05% Tween 20 in PBS), phosphorylated PGT level is determined. By aspirating out the antibody, the plate is cleaned four times using wash buffer. Tentamethylbenzidine Microwell Peroxidase Substrate, 50 μL/well, is added to develop the colorimetric signal.50 μL/well of sulfuric acid, 0.09 m, is added to stop the signal. By measuring the absorbance at 450 nm, the phosphotyrosine product formed is estimated. In wells lacking ATP, kinase protein, or PGT, the signal for controls is usually A0.6–1.2, is proportional to the incubation period of 6 minutes, and has almost no background.
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Cell Assay |
In 24-well plates, cells are seeded in duplicate, with 5~10 × 103 per well. The following day, CP-724,714 is added by titrating at least six dilutions, ranging from 0.1 nM to 10 μM. Additionally, control wells devoid of CP-724,714 are seeded. After six to seven days of growth, the number of surviving cells is determined. Cells are trypsinized, then immediately counted using a Coulter Z2 particle counter and put in isotone solution. For every concentration, the calculation of growth inhibition is expressed as [(1− experimental value / control value) × 100]. Dose-response curves are averaged after being repeated at least twice. Calcusyn software is used to calculate IC50 values.
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Animal Protocol |
FRE-erbB2 BT-474, MDA-MB-453, MDA-MB-231, LoVo (colon), and Colo-205 (colon) xenografts are established in athymic female mice (CD-1 nu/nu).
~100 mg/kg. Administered via p.o. |
References |
Molecular Formula |
C27H27N5O3
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Molecular Weight |
469.53
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CAS # |
537705-08-1
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SMILES |
O=C(NC/C=C/C1=CC2=C(NC3=CC=C(OC4=CC=C(C)N=C4)C(C)=C3)N=CN=C2C=C1)COC
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InChi Key |
LLVZBTWPGQVVLW-SNAWJCMRSA-N
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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+
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Chemical Name |
(E)-2-methoxy-N-(3-(4-(3-methyl-4-(6-methylpyridin-3-yloxy)phenylamino)quinazolin-6-yl)allyl)acetamide.
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Synonyms |
CP 724714; CP-724714; CP724714
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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)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00055926 | Completed | Drug: CP-724,714 | Breast Cancer | Jonsson Comprehensive Cancer Center | January 2003 | Phase 1 |
NCT00102895 | Terminated | Drug: CP-724,714 | Breast Neoplasms Neoplasm Metastasis |
Pfizer | April 2005 | Phase 2 |
A, selective inhibition of erbB2 kinase by CP-724,714. td> |
Effect of CP-724,714 on the growth of tumor xenografts. Cancer Res. 2007 Oct 15;67(20):9887-93. td> |
Effect of CP-724,714 on phospho-Erk and phospho-Akt in BT-474 xenografts. Cancer Res. 2007 Oct 15;67(20):9887-93. td> |