| Size | Price | Stock | Qty |
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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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CP-547632 HCl (PAN90806), a novel isothiazole, is a 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 hydrochloride (1-1000 nM; 1 hour) suppresses VEGF-stimulated VEGFR-2 phosphorylation in a dose-adjusted manner with an IC50 value of 6 nM [1].
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| ln Vivo |
CP-547632 hydrochloride (sidewall; 6.25-100 mg/kg/day; duration 10-24 days) creates a dosage modifying factor in the growth of Colo-205, DLD-1, and MDA-MB-231 xenografts [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 |
Animal/Disease Models: H-ras tumor-bearing mice [1]
Doses: 50 mg/kg Route of Administration: Oral Experimental Results:After a single oral dose of 50 mg/kg, the plasma concentration was higher than 500 ng/ml within 12 hrs (hrs (hours)). |
| References |
[1]. Beebe JS, et al. Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy. Cancer Res. 2003 Nov 1;63(21):7301-9.
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| Molecular Formula |
C₂₀H₂₅BRCLF₂N₅O₃S
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|---|---|
| Molecular Weight |
568.86
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| Exact Mass |
567.05
|
| Elemental Analysis |
C, 42.23; H, 4.43; Br, 14.05; Cl, 6.23; F, 6.68; N, 12.31; O, 8.44; S, 5.64
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| CAS # |
252003-71-7
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| Related CAS # |
CP-547632;252003-65-9;CP-547632 TFA;2805804-54-8
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| Appearance |
Solid powder
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| SMILES |
C1CCN(C1)CCCCNC(=O)NC2=C(C(=NS2)OCC3=C(C=C(C=C3F)Br)F)C(=O)N.Cl
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| InChi Key |
NNPJZJJMQDXYGN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H24BrF2N5O3S.ClH/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);1H
|
| Chemical Name |
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide;hydrochloride
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| Synonyms |
PAN90806 HCl; 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: ~33.3 mg/mL (~58.6 mM)
H2O: ~1 mg/mL (~1.8 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.39 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 (4.39 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.39 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 | 1.7579 mL | 8.7895 mL | 17.5790 mL | |
| 5 mM | 0.3516 mL | 1.7579 mL | 3.5158 mL | |
| 10 mM | 0.1758 mL | 0.8790 mL | 1.7579 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.
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