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| 10mg |
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| 25mg |
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| 50mg |
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| 250mg |
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Purity: ≥98%
CP-547632 (PAN-90806), a novel isothiazole, is a novel, orally bioavailable and ATP-competitive inhibitor of the VEGFR-2 and basic fibroblast growth factor (FGF) kinases with IC50s of 11 nM and 9 nM, respectively. It exhibits selectivity in comparison to other related TKs such as platelet-derived growth factor beta and epidermal growth factor receptor. Additionally, in a whole cell assay, it inhibits VEGF-stimulated autophosphorylation of VEGFR-2 at an IC(50) value of 6 nM. VEGFR-2 phosphorylation in tumors was inhibited in a dose-dependent manner (EC(50) = 590 ng/ml) following oral administration of CP-547,632 to mice harboring NIH3T3/H-ras tumors. These concentrations of plasma showed a strong correlation with the measured levels of the substance required to prevent VEGF-induced corneal angiogenesis in BALB/c mice. CP-547,632 is a compound that potently inhibits both basic FGF and VEGF-induced angiogenesis in vivo. The inhibitory activities of this compound were directly compared against FGF receptor 2 or VEGFR-2 using a sponge angiogenesis assay. After giving this medication once daily intraperitoneally to athymic mice carrying human xenografts, the antitumor efficacy was assessed and showed up to 85% tumor growth inhibition. A well-tolerated, orally bioavailable inhibitor called CP-547,632 is currently being studied in clinical trials to treat cancers in humans.
| Targets |
VEGFR-2 (IC50 = 11 nM); FGFR (IC50 = 9 nM)
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|---|---|
| ln Vitro |
CP-547632 (1-1000 nM; 1 hour) has an IC50 value of 6 nM and suppresses VEGF-stimulated VEGFR-2 phosphorylation in a dose-dependent manner [1].
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| ln Vivo |
CP-547632 (1-1000 nM; 1 hours)inhibits VEGF-stimulated VEGFR-2 phosphorylation in a dose-dependent manner, with an IC50 value of 6 nM[1].
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| Enzyme Assay |
CP-547632 (p.o.; 6.25-100 mg/kg/day; for 10-24 days) nhibits Colo-205, DLD-1, and MDA-MB-231 xenografts' ability to grow in a dose-dependent manner[1]. For 12 hours, plasma concentrations of CP-547632 (oral; 50 mg/kg; single oral dose) are greater than 500 ng/ml[1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Serum-depleted Cell Tested Concentrations: 1, 4, 16, 63, 250, 1000 nM Incubation Duration: 1 hour Experimental Results: Inhibits VEGF-stimulated VEGFR-2 phosphorylation in a dose-dependent manner. |
| Animal Protocol |
Athymic female mice (CD-1 nu/nu) bearing tumors (75-150 mm in size)[1]
6.25, 12.5, 25, 50, 100 mg/kg PO; daily; 10-24 days |
| References | |
| Additional Infomation |
CP-547632 has been used in trials studying the treatment of Ovarian Cancer, Lung Neoplasms, Ovarian Neoplasms, Peritoneal Neoplasms, and Fallopian Tube Cancer, among others.
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| Molecular Formula |
C20H24BRF2N5O3S
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|---|---|
| Molecular Weight |
532.40206
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| Exact Mass |
531.075
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| Elemental Analysis |
C, 45.12; H, 4.54; Br, 15.01; F, 7.14; N, 13.15; O, 9.02; S, 6.02
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| CAS # |
252003-65-9
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| Related CAS # |
CP-547632 hydrochloride;252003-71-7;CP-547632 TFA;2805804-54-8
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| PubChem CID |
9811611
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| Appearance |
White to light yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
548.6±50.0 °C at 760 mmHg
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| Flash Point |
285.6±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.622
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| LogP |
3.69
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
32
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| Complexity |
622
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NC1=C(C(N)=O)C(OCC2=C(F)C=C(Br)C=C2F)=NS1)NCCCCN3CCCC3
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| InChi Key |
HXHAJRMTJXHJJZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H24BrF2N5O3S/c21-12-9-14(22)13(15(23)10-12)11-31-18-16(17(24)29)19(32-27-18)26-20(30)25-5-1-2-6-28-7-3-4-8-28/h9-10H,1-8,11H2,(H2,24,29)(H2,25,26,30)
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| Chemical Name |
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide
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| Synonyms |
PAN90806; PAN 90806; PAN-90806; CP547632; CP 547632; CP-547632; CP632; OSI632; CP 632; OSI 632; CP-632; OSI-632
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO: ~100 mg/mL (~187.8 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 4 mg/mL (7.51 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 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: 4 mg/mL (7.51 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 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. View More
Solubility in Formulation 3: ≥ 4 mg/mL (7.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8783 mL | 9.3914 mL | 18.7829 mL | |
| 5 mM | 0.3757 mL | 1.8783 mL | 3.7566 mL | |
| 10 mM | 0.1878 mL | 0.9391 mL | 1.8783 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 |
| NCT00096239 | Completed | Drug: CP-547,632 | Fallopian Tube Cancer Ovarian Cancer |
Jonsson Comprehensive Cancer Center |
December 2004 | Phase 2 |
| NCT00074854 | Completed | Drug: CP-547,632 | Lung Neoplasms | Pfizer | May 2002 | Phase 1 Phase 2 |
| NCT00074867 | Completed | Drug: CP-547,632 | Ovarian Neoplasms Peritoneal Neoplasms |
Pfizer | October 2003 | Phase 2 |
 Lineweaver Burke plot of ATP competition. Inhibition of kinase autophosphorylation with CP-547,632. Phospho-VEGFR-2 in cell-based assay. CP-547,632 inhibits VEGF-stimulated phosphorylation in cells with an IC50value of 6 nm.Cancer Res. 2003 Nov 1;63(21):7301-9. |
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 Effect of CP-547,632 on the growth of human tumorsin vivo.Cancer Res. 2003 Nov 1;63(21):7301-9. |
 Pharmacokinetic and pharmacodynamic evaluation of CP-547,632 after a single oral dose (50 mg/kg) in H-rastumor-bearing mice.
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