K134 is a phosphodiesterase 3 (PDE3) inhibitor. Inhibition of PDE3A, PDE3B, PDE5, PDE2, PDE4 and IC50 are 0.1, 0.28, 12.1, >300 and >300 μM respectively.

Physicochemical Properties

Molecular Formula	C22H29N3O4
Molecular Weight	399.491
Exact Mass	399.216
CAS #	189362-06-9
PubChem CID	9908900
Appearance	White to off-white solid powder
LogP	2.978
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	29
Complexity	621
Defined Atom Stereocenter Count	2
SMILES	C1CC[C@H]([C@@H](C1)N(C2CC2)C(=O)NCCCOC3=CC4=C(C=C3)NC(=O)C=C4)O
InChi Key	ULGNGSQNNMKROG-WOJBJXKFSA-N
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
Chemical Name	1-cyclopropyl-1-[(1R,2R)-2-hydroxycyclohexyl]-3-[3-[(2-oxo-1H-quinolin-6-yl)oxy]propyl]urea
Synonyms	K134; OPC-33509; K-134
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
References	[1]. K-134, a phosphodiesterase 3 inhibitor, prevents brain damage by inhibiting thrombus formation in a rat cerebral infarction model. PLoS One. 2012;7(10):e46432.
Additional Infomation	K-134 has been used in trials studying the treatment of Intermittent Claudication.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~125.16 mM)

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.