| Size | Price | Stock | Qty |
|---|---|---|---|
| 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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| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Phosphodiesterase 4 subtype D (PDE4-D) with IC50 = 3 nM; also inhibits PDE4-A (IC50 = 310 nM), PDE4-B (IC50 = 287 nM), and PDE4-C (IC50 = 3858 nM), showing ≥96- to 1286-fold selectivity for PDE4-D over other subtypes. Inactive on PDE1-3 and PDE5-11 (IC50s >5000 nM). [2]
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| ln Vitro |
MRP2 and BCRP were found to be substrates of CP-671,305, but not MDR1. While CP-671,305 is not a substrate of human OATP1B1 or OATP1B3, it is a high affinity substrate of human OATP2B1 (Km=4 μM). High affinity (Km=12 μM) for rat liver Oatp1a4 is demonstrated by CP-671,305[1]. CP-671,305 does not show competitive inhibition (IC50 > 50 μM) against CYP1A2, 2C9, 2C19, 2D6, and 3A4, the five major cytochrome P450 enzymes. Similarly, CP-671,305 did not cause any of the five major cytochrome P450 enzymes to become inactive over time [2].
CP-671,305 potently inhibits the production of leukotriene E4 from eosinophils in Sephadex bead-stimulated human whole blood with an IC50 = 52 nM. [2] It also potently inhibits the release of leukotriene B4 from neutrophils in Ca²⁺ ionophore-challenged blood with an IC50 = 106 nM. [2] In liver microsomes and hepatocytes from rat, dog, monkey, and human, CP-671,305 was stable (half-life >4 h); no metabolites, including potentially reactive acyl glucuronide or catechol/quinone intermediates, were detected even at high concentrations (100 μM) and in the presence of glutathione. [2] CP-671,305 did not exhibit competitive inhibition of the five major cytochrome P450 enzymes (CYP1A2, 2C9, 2C19, 2D6, and 3A4) with IC50 values >50 μM, nor did it show time-dependent inactivation of these enzymes. [2] |
| ln Vivo |
CP-671,305 exhibits generally good pharmacokinetic properties, with systemic plasma clearance rates in Sprague-Dawley rats (9.60 ± 1.16 mL/min/kg) and beagle dogs (2.90 ± 0.81 mL/min/kg) after intravenous injection and lower in cynomolgus monkeys (2.94 ± 0.87 mL/min/kg) resulting in a plasma half-life > 5 hours. Following oral administration, moderate to high bioavailability was observed in rats (43-80%), dogs (45%), and monkeys (26%). In rats, oral pharmacokinetics are dose-dependent over the dose range studied (10 and 25 mg/kg) [2].
After subcutaneous administration to cynomolgus monkeys, CP-671,305 inhibits antigen-induced pulmonary eosinophil influx in a dose-dependent fashion (exact doses and inhibition percentages not specified). [2] |
| Animal Protocol |
For intravenous (i.v.) dosing, CP-671,305 was formulated in glycerol formal. For oral (p.o.) dosing, it was given as a suspension in 0.5% methylcellulose. [2]
In Sprague-Dawley rats: i.v. dose 20 mg/kg, p.o. doses 10 and 25 mg/kg; blood samples via jugular vein; urine and bile collected for 24 h. [2] In beagle dogs: i.v. dose 3 mg/kg, p.o. dose 0.5 mg/kg; also i.v. 3.7 mg/kg in bile duct-exteriorized dogs; blood samples via jugular vein; urine and bile collected 0-24 h. [2] In cynomolgus monkeys: i.v. dose 5 mg/kg, p.o. dose 3 mg/kg; blood samples via femoral vein; urine and bile collected 0-48 h. [2] |
| ADME/Pharmacokinetics |
In rats: i.v. (20 mg/kg) showed low plasma clearance (9.60±1.16 ml/min/kg), low steady-state volume of distribution (0.82±0.47 L/kg), elimination half-life 5.6 h; oral bioavailability 45-80% (10 and 25 mg/kg). [2]
In bile duct-cannulated rats, clearance increased 1.6-fold (p<0.05) and half-life decreased to 1.03 h; unchanged drug accounted for 50-60% of the dose in bile. About 10% of dose excreted unchanged in urine; unbound renal clearance (4.56±1.49 ml/min/kg) lower than glomerular filtration rate. [2] In dogs: i.v. (3 mg/kg) showed CLp 2.90±0.81 ml/min/kg, Vdss 0.55±0.30 L/kg, half-life 5.9 h; oral bioavailability 45% at 0.5 mg/kg; unchanged drug ~12% in bile; unbound renal clearance 0.36±0.23 ml/min/kg. [2] In monkeys: i.v. (5 mg/kg) showed CLp 2.94±0.87 ml/min/kg, Vdss 1.2±0.2 L/kg, half-life 13.1 h; oral bioavailability 26% at 3 mg/kg. [2] Plasma protein binding >97% in rat, dog, monkey, and human at 800-1600 ng/ml, with no significant species difference. [2] No metabolites detected in plasma, urine, or bile after i.v./p.o. dosing in any species. [2] |
| References |
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| Additional Infomation |
CP-671,305 is a PDE4-D selective inhibitor that acts as an anti-inflammatory agent by blocking cAMP-regulated production and release of mediators from neutrophils and eosinophils. The compound is resistant to metabolism, and its principal route of clearance in rats and dogs is renal and biliary excretion of unchanged drug. The presence of a carboxylic acid and 1,3-benzodioxole substituents raised potential concerns for reactive acyl glucuronide or catechol/quinone formation, but no such metabolites were observed. The compound does not inhibit or inactivate major CYP enzymes, suggesting low risk for drug-drug interactions. Predicted human pharmacokinetics using allometric scaling suggest low clearance (1.6 ml/min/kg with protein binding correction) and low volume of distribution, comparable to cilomilast. [2]
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| Molecular Formula |
C23H19FN2O7
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|---|---|
| Molecular Weight |
454.40
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| Exact Mass |
454.117
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| CAS # |
445295-04-5
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| PubChem CID |
9955578
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
664.1±55.0 °C at 760 mmHg
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| Flash Point |
355.4±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.617
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| LogP |
3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
683
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C(=O)O)OC1=CC(=C(C=C1)CNC(=O)C2=C(N=CC=C2)OC3=CC4=C(C=C3)OCO4)F
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| InChi Key |
CNIGFESSDPOCKS-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C23H19FN2O7/c1-13(23(28)29)32-15-5-4-14(18(24)9-15)11-26-21(27)17-3-2-8-25-22(17)33-16-6-7-19-20(10-16)31-12-30-19/h2-10,13H,11-12H2,1H3,(H,26,27)(H,28,29)/t13-/m1/s1
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| Chemical Name |
(R)-2-(4-((((2-((Benzo(1,3)dioxol-5-yl)oxy)pyridin-3-yl)carbonyl)amino)methyl)-3-fluorophenoxy)propionic acid
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| Synonyms |
CP-671305; CP 671305; CP671305; UNII-9LH034R9R9.
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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 |
| 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 (~220.07 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.50 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 (5.50 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 (5.50 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 | 2.2007 mL | 11.0035 mL | 22.0070 mL | |
| 5 mM | 0.4401 mL | 2.2007 mL | 4.4014 mL | |
| 10 mM | 0.2201 mL | 1.1004 mL | 2.2007 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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