| 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 | |||
| Other Sizes |
| Targets |
VEGFR-2 (IC50 = 11 nM); FGFR (IC50 = 9 nM)
The primary targets of CP-547632 hydrochloride are VEGFR-2 (also known as KDR/Flk-1) and basic fibroblast growth factor (FGF) kinases. VEGFR-2 is a receptor tyrosine kinase that mediates VEGF-induced angiogenesis, which is essential for tumor growth and metastasis. FGF kinases are also involved in angiogenesis and tumor progression. CP-547632 hydrochloride is an ATP-competitive inhibitor, meaning it competes with ATP for binding to the kinase domain of these receptors, thereby blocking their phosphorylation and downstream signaling. By inhibiting both VEGFR-2 and FGF kinases, the compound exerts a dual anti-angiogenic effect, making it a promising therapeutic agent for cancer and other angiogenesis-related diseases. |
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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].
In vitro, CP-547632 hydrochloride potently inhibits VEGFR-2 and FGF kinase activity with IC50 values of 11 nM and 9 nM, respectively. It is more selective for VEGFR-2 and bFGF over EGFR, PDGFRbeta, and related tyrosine kinases. The compound inhibits VEGF- and bFGF-induced angiogenesis in cell-based assays. It also inhibits the proliferation of endothelial cells stimulated by VEGF or bFGF. CP-547632 hydrochloride has been shown to effectively inhibit the growth of various cancer cell lines in vitro, although its primary mechanism of action is anti-angiogenic rather than direct cytotoxic. Its potent and selective inhibition of key angiogenic kinases makes it a valuable tool for studying angiogenesis in vitro. |
| 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 ].
In vivo, CP-547632 hydrochloride has demonstrated strong preclinical efficacy in reducing tumor vascularization and growth. It inhibits VEGF- and bFGF-induced angiogenesis in animal models. The compound inhibits the growth of xenograft tumors in mice. In pharmacokinetic studies, oral administration of CP-547632 hydrochloride at 50 mg/kg yields plasma concentrations above 500 ng/mL for 12 hours, indicating sustained drug exposure. The compound is well-tolerated in animal models, with no significant adverse effects reported at therapeutic doses. Its antitumor efficacy and favorable pharmacokinetic profile make it a promising candidate for further development. |
| Enzyme Assay |
The in vitro kinase activity of CP-547632 hydrochloride can be assessed using cell-free enzyme assays. A typical protocol involves incubating the compound with recombinant VEGFR-2 or FGF kinase, ATP, and a peptide substrate in a kinase buffer. The reaction is carried out at 30degC for 30-60 minutes. The amount of phosphorylated substrate is then measured using a kinase activity assay kit, such as a luminescent ATP detection assay or a radioactive filter-binding assay. The IC50 value is determined by plotting the percentage of kinase activity remaining against the compound concentration. The selectivity of the compound can be assessed by testing its activity against a panel of related kinases, such as EGFR, PDGFRbeta, and other tyrosine kinases.
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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. For in vitro cellular experiments, cells (e.g., endothelial cells, cancer cells) are cultured in appropriate media and treated with CP-547632 hydrochloride at various concentrations (typically 0.1-100 microM). Cells are stimulated with VEGF or bFGF, and downstream signaling pathways, such as ERK and AKT phosphorylation, are assessed by Western blot. Cell proliferation is measured using MTT or BrdU incorporation assays. Angiogenesis can be assessed using tube formation assays on Matrigel, where endothelial cells are seeded on Matrigel-coated plates, and the formation of capillary-like structures is quantified after 6-18 hours of incubation with the compound. The duration of treatment and concentration of the compound can be optimized depending on the cell type and the specific experimental objectives. |
| 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)). In vivo animal experiments with CP-547632 hydrochloride typically involve oral administration in mice or rats. A common dosing regimen is 25-100 mg/kg, administered once or twice daily. For xenograft studies, tumor-bearing mice are treated with the compound, and tumor growth is monitored by caliper measurements. The compound's effect on angiogenesis is assessed by measuring tumor vascular density using immunohistochemical staining for CD31 or other endothelial markers. Pharmacokinetic studies are performed by collecting blood samples at various time points after dosing and measuring plasma drug concentrations by LC-MS/MS. The compound is formulated in suitable vehicles such as PEG-400 or carboxymethylcellulose. |
| ADME/Pharmacokinetics |
CP-547632 hydrochloride is an orally bioavailable compound with favorable pharmacokinetic properties. Following oral administration, it is rapidly absorbed and achieves therapeutic plasma concentrations. At a dose of 50 mg/kg, plasma concentrations remain above 500 ng/mL for 12 hours. The compound is metabolized in the liver and excreted in the bile and urine. Its oral bioavailability is sufficient to support once- or twice-daily dosing in animal models. The compound's pharmacokinetic profile is characterized by dose-dependent exposure and a moderate half-life. It is well-tolerated in preclinical species, with no significant accumulation or toxicity at therapeutic doses.
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| Toxicity/Toxicokinetics |
CP-547632 hydrochloride is well-tolerated in preclinical animal models at therapeutic doses. No significant adverse effects have been reported at doses that achieve efficacious plasma concentrations. In vitro, the compound shows selectivity for VEGFR-2 and bFGF over other kinases, suggesting a low risk of off-target toxicity. However, as with any kinase inhibitor, potential toxicities may include effects on normal angiogenesis, wound healing, and vascular function. Long-term safety studies are needed to fully characterize its toxicity profile. The compound should be handled with standard laboratory precautions and is intended for research use only.
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| References | |
| Additional Infomation |
CP-547632 hydrochloride (PAN-90806) is a novel isothiazole compound that acts as a potent and orally bioavailable inhibitor of VEGFR-2 and FGF kinases. It exhibits IC50 values of 11 nM for VEGFR-2 and 9 nM for FGF kinases. The compound is selective for VEGFR-2 and bFGF over EGFR, PDGFRbeta, and related tyrosine kinases. CP-547632 hydrochloride has shown strong preclinical efficacy in reducing tumor vascularization and growth. It inhibits VEGF- and bFGF-induced angiogenesis in animal models and inhibits the growth of xenograft tumors in mice. The compound has been studied for its potential in treating cancer and other angiogenesis-related diseases. It is available as a research compound and is not approved for clinical use.
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| Molecular Formula |
C20H25BRCLF2N5O3S
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|---|---|
| Molecular Weight |
568.863008260727
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| Exact Mass |
567.05
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| 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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| PubChem CID |
10370762
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| Appearance |
White to light yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
33
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| Complexity |
622
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| Defined Atom Stereocenter Count |
0
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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
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| 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) |
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| 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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