BAY-60-7550

Biological Activity

BAY-60-7550 is a potent Type 2 cyclic nucleotide phosphodiesterases (PDE2) inhibitor with IC50 values of 2.0 nM (bovine) and 4.7 nM (human). BAY-60-7550 is an analog of EHNA, which is more than 100-fold more potent and is highly selective for PDE2A.

Customer Product Validations & Biological Datas

	Source	Neurobiol Aging (2015). Figure 1. BAY-60-7550
	Method	i.v.
	Cell Lines	mice
	Concentrations	3 mg/kg
	Incubation Time	24 h
	Results	Bay 60-7550-treated mice (3 mg/kg) took significantly less time to reach the platform position, and made more crossings over the platform, than stressed mice

Protocol

Cell Experiment
Cell lines	human distal pulmonary artery smooth muscle cells
Preparation method	Cell proliferation. Growth of human distal pulmonary artery smooth muscle cells isolated from patients with idiopathic pulmonary arterial hypertension (IPAH) or control cells from adults undergoing transplant or lung resection for suspected malignancy, were monitored as we have described previously 29 following treatment with BAY 60-7550 (1μmol/L), ANP (1μmol/L), DETA-NONOate (10μmol/L), or treprostinil (1μmol/L), alone or in combination.
Concentrations	1μmol/L
Incubation time	unknow

Animal Experiment
Animal models	Oxidative Stress on Behavior in mice
Formulation	dissolved in 50% dimethyl sulfoxide (Fisher Scientific Co., Pittsburgh, PA)
Dosages	3 mg/kg; given 30 min before each BSO treatment
Administration	i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

Inhibition of phosphodiesterase 2 augments cGMP and cAMP signaling to ameliorate pulmonary hypertension.
Bubb KJ, et al. Circulation. 2014 Aug 5;130(6):496-507. PMID: 24899690.

Phosphodiesterase-2 inhibitor reverses corticosterone-induced neurotoxicity and related behavioural changes via cGMP/PKG dependent pathway.
Xu et al. Int J Neuropsychopharmacol. 2012 Jul 31;1-13. PMID: 22850435.

Mechanisms of carbon monoxide attenuation of tubuloglomerular feedback.
Ren et al. Hypertension. 2012 Jun;59(6):1139-44. PMID: 22508834.

Selective phosphodiesterase inhibitors improve performance on the ED/ID cognitive task in rats
Rodefer et al. Neuropharmacology. 2012 Mar;62(3):1182-90. PMID: 21856317.

PDE5A suppression of acute beta-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation.
Lee et al. Basic Res Cardiol. 2010 May;105(3):337-47. PMID: 20107996.

Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice.
Masood A, et al. J Pharmacol Exp Ther. 2008 Aug;326(2):369-79. PMID: 18456873.