| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
PDE3A and PDE3B (phosphodiesterase 3 isoforms). K-134 also inhibits PDE5 with lower potency, and shows negligible inhibition of PDE2 and PDE4. The compound is a selective PDE3 inhibitor with significantly higher potency against PDE3 compared to other PDE family members.
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| ln Vitro |
In vitro, K134 (K-134) suppresses rat platelet aggregation that is caused by collagen and ADP in a dose-dependent manner. K134 exhibited half-maximal (50%) inhibitory concentration (IC50) values of 2.5 µM and 3.2 µM, in that order. K134 also prevented mice's platelet aggregation in vitro, with dose-dependent IC50 values of 5.5 µM and 6.7 µM for collagen and ADP, respectively [1].
K-134 shows IC50 values of 0.1 µM for PDE3A and 0.28 µM for PDE3B. It inhibits PDE5 with an IC50 of 12.1 µM, and shows IC50 >300 µM for both PDE2 and PDE4. K-134 inhibits mouse platelet aggregation induced by collagen and ADP in a dose-dependent manner with IC50 values of 5.5 µM and 6.7 µM, respectively. It also inhibits rat platelet aggregation in vitro. |
| ln Vivo |
In a stroke model, K134 (K-134) significantly delayed middle cerebral artery (MCA) occlusion time at dosages >10 mg/kg and reduced cerebral infarct size at 30 mg/kg (n = 12, 87.5±5.6 vs. 126.8± 7.5 mm3, P<0.01), demonstrating that it has a strong anti-thrombotic action. The total bleeding risk of K134 is typically studied in mice. A single oral dose of 30 mg/kg K134 did not prolong bleeding duration compared with controls (106±5 seconds vs. 110±5 seconds, not significant). Furthermore, sufficiently high plasma concentrations of K134 (13.6 ± 2.3 μM) to suppress platelet aggregation were identified 10 minutes after a single 30 mg/kg dosage in mice, the same time point as in the preceding tests. Bleeding time. Next, the effect of PDE3 inhibitors on thrombosis was also examined in a rat arteriovenous shunt model. K134 can greatly lower the incidence of occlusive shunt thrombosis at dosages higher than 10 mg/kg (half maximum effective dose: ED50=11 mg/kg). At a dosage of 10 mg/kg, the plasma concentration of K134 is 0.43±0.08 µM (Cmax)[1].
K-134 inhibits rat and mouse platelet aggregation induced by collagen and ADP in a dose-dependent manner in vitro. Detailed in vivo activity data including animal models, administration routes, and pharmacodynamic effects has not been extensively reported in the available literature. Further in vivo studies would be needed to evaluate its antiplatelet and cardiovascular effects. |
| Enzyme Assay |
PDE enzymatic activity assay: Recombinant human PDE3A, PDE3B, PDE5, PDE2, or PDE4 is incubated with varying concentrations of K-134 and 1 µM cAMP or cGMP as substrate in assay buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 0.1 mg/mL BSA) at 30°C for 30 min. The reaction is terminated by boiling, and the product is converted to AMP or GMP by snake venom 5'-nucleotidase. The amount of phosphate released is measured by a colorimetric method or using a scintillation proximity assay with [³H]-labeled substrate. IC50 values are calculated.
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| Cell Assay |
Platelet aggregation assay: Mouse or rat platelets are isolated from whole blood by centrifugation and adjusted to a concentration of 3×10⁸ platelets/mL. Platelet-rich plasma is pre-incubated with varying concentrations of K-134 (0.1-100 µM) for 5 min at 37°C. Platelet aggregation is induced by the addition of collagen (2 µg/mL) or ADP (10 µM). Aggregation is monitored using a platelet aggregometer by measuring light transmission over 5-10 min. IC50 values for inhibition of aggregation are calculated from dose-response curves.
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| Animal Protocol |
No detailed in vivo animal experimental protocols have been published in the available literature. In vivo studies would typically involve mouse or rat thrombosis models, where K-134 would be administered via oral or intravenous routes, followed by measurement of platelet aggregation ex vivo, bleeding time, and thrombus formation in arterial or venous injury models.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data has been published in the available literature. K-134 has a molecular formula and weight consistent with small-molecule PDE inhibitors. Comprehensive PK parameters such as oral bioavailability, half-life, Cmax, and plasma protein binding remain to be characterized. The compound is available as a solid for research use.
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| Toxicity/Toxicokinetics |
No toxicity data has been published in the available literature. K-134 is for research use only and not for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound. As with all PDE inhibitors, potential cardiovascular effects should be considered.
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| References | |
| Additional Infomation |
K-134 has been used in trials investigating the treatment of intermittent claudication.
K-134 is a selective PDE3 inhibitor with IC50 values of 0.1 µM (PDE3A) and 0.28 µM (PDE3B). It shows ~120-fold selectivity for PDE3A over PDE5 (IC50 = 12.1 µM) and >3000-fold over PDE2 and PDE4. Inhibition of PDE3 increases cAMP levels. K-134 inhibits platelet aggregation induced by collagen and ADP. No clinical trials or approved上市 status have been reported. |
| Molecular Formula |
C22H29N3O4
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|---|---|
| Molecular Weight |
399.491
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| Exact Mass |
399.216
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| CAS # |
189362-06-9
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| PubChem CID |
9908900
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| Appearance |
White to off-white solid powder
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| LogP |
2.978
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
621
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CC[C@H]([C@@H](C1)N(C2CC2)C(=O)NCCCOC3=CC4=C(C=C3)NC(=O)C=C4)O
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| InChi Key |
ULGNGSQNNMKROG-WOJBJXKFSA-N
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| InChi Code |
InChI=1S/C22H29N3O4/c26-20-5-2-1-4-19(20)25(16-7-8-16)22(28)23-12-3-13-29-17-9-10-18-15(14-17)6-11-21(27)24-18/h6,9-11,14,16,19-20,26H,1-5,7-8,12-13H2,(H,23,28)(H,24,27)/t19-,20-/m1/s1
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| Chemical Name |
1-cyclopropyl-1-[(1R,2R)-2-hydroxycyclohexyl]-3-[3-[(2-oxo-1H-quinolin-6-yl)oxy]propyl]urea
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| Synonyms |
K134; OPC-33509; K-134
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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 and light. |
| 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 : ~50 mg/mL (~125.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.26 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5032 mL | 12.5160 mL | 25.0319 mL | |
| 5 mM | 0.5006 mL | 2.5032 mL | 5.0064 mL | |
| 10 mM | 0.2503 mL | 1.2516 mL | 2.5032 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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