Pardoprunox (formerly known as SLV-308, DU-126891 or SME-308) is novel & potent dopamine D2/5-HT1A receptor agonist that has the potential for the treatment of Parkinson's disease. Pardoprunox functions by binding to 5-HT(1) (A) and dopamine D(2), D(3), and D(4) receptors.It is a full agonist at serotonin 5-HT(1) (A) receptors and a partial agonist at dopamine D(2) and D(3) receptors. SLV308 functioned as a strong but partial D(2) receptor agonist at cloned human dopamine D(2,L) receptors (pEC(50) = 8.0 and pA(2) = 8.4) with a 50% efficacy on forskolin stimulated cAMP accumulation. SLV308 functioned as a partial agonist at human recombinant dopamine D(3) receptors, inducing [(35)S]GTPgammaS binding (intrinsic activity of 67%; pEC(50) = 9.2) and inhibiting the dopamine-induced [(35)S]GTPgammaS binding (pA(2) = 9.0). SLV308 had low potency (pEC(50) = 6.3) but nonetheless functioned as a complete 5-HT(1) (A) receptor agonist on forskolin-induced cAMP accumulation at cloned human 5-HT(1) (A) receptors.

Physicochemical Properties

Molecular Formula	C12H16CLN3O2
Molecular Weight	269.73
Exact Mass	269.093
Elemental Analysis	C, 53.44; H, 5.98; Cl, 13.14; N, 15.58; O, 11.86
CAS #	269718-83-4
Related CAS #	Pardoprunox; 269718-84-5
PubChem CID	6918524
Appearance	Off-white to pink pale mauve solid powder
LogP	2.09
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	18
Complexity	302
Defined Atom Stereocenter Count	0
SMILES	O=C1OC2=C(N3CCN(C)CC3)C=CC=C2N1.[H]Cl
InChi Key	NQRIKTDKFHAOKC-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H15N3O2.ClH/c1-14-5-7-15(8-6-14)10-4-2-3-9-11(10)17-12(16)13-9;/h2-4H,5-8H2,1H3,(H,13,16);1H
Chemical Name	7-(4-methylpiperazin-1-yl)-3H-1,3-benzoxazol-2-one;hydrochloride
Synonyms	Pardoprunox; Pardoprunox HCl; SLV-308 HCl; SLV 308; SLV308; DU-126891 HCl; DU126891; DU 126891; SME-308 HCl; SME308; SME308
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, 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)

Biological Activity

Targets	5-HT1A Receptor ( pEC50 = 6.3 ); D2 Receptor ( pEC50 = 8 ); D3 Receptor ( pEC50 = 9.2 nM )
ln Vitro	Pardoprunox (SLV-308) hydrochloride has a 50% efficacy on forskolin-stimulated cAMP accumulation and functions as a strong but partial D2 receptor agonist (pEC50= 8.0 and pA2= 8.4). Pardoprunox hydrochloride antagonizes the dopamine-induced [(35)S]GTPgammaS binding (pA2=9.0) and functions as a partial agonist at human recombinant dopamine D3 receptors, inducing [(35)S]GTPgammaS binding with an intrinsic activity of 67%. On forskolin-induced cAMP accumulation at cloned human 5-HT1A receptors, pardoprunox hydrochloride functions as a full 5-HT1A receptor agonist, albeit with low potency (pEC50=6.3)[1].
ln Vivo	Pardoprunox causes rats with unilateral 6 to exhibit contralateral turning behavior.-lesion of the substantia nigra pars compacta (SNpc) caused by hydroxydopamine (MED=0.03 mg/kg; po). Pardoprunox dose-dependently reduces motor disability (MED=0.03mg/kg; po) and increases locomotor activity (MED=0.03mg/kg; po) in common marmosets receiving MPTP treatment. On the other hand, pardoprunox reduced the amount of rodents that were able to move in a novelty-induced manner (MED=0.01 mg/kg; po), hyperlocomotion (MED=0.3 mg/kg; po), and climbing (MED=0.6 mg/kg; po) induced by (+)-amphetamine. Additionally, 5-HT1A receptor-mediated behaviors such as lower lip retraction and flat body posture are induced by pardoprunox (MED=0.3mg/kg; po). All together, these results show that pardoprunox decreases parkinsonism in animal models and has partial agonist effects on dopamine D2/3 and 5-HT1A. partial agonist activity at the functional D2 receptor and is successful in models that predict efficacy in Parkinson's disease
Enzyme Assay	Pardoprunox also exhibits a lower affinity for binding to D4 (pKi = 7.8), α1-adrenergic (pKi = 7.8), α2-adrenergic (pKi = 7.4), and 5-HT7 receptors (pKi = 7.2). With a 50% efficacy on forskolin-stimulated cAMP accumulation, pardoprunox exerts a strong but partial D(2) receptor agonist (pEC50 = 8.0 and pA2 = 8.4). Pardoprunox inhibits the dopamine-induced induction of [35S]GTPgammaS binding (pA2 = 9.0) and functions as a partial agonist at human recombinant dopamine D3 receptors, where it induces [35S]GTPgammaS binding with an intrinsic activity of 67%. While cloned human 5-HT1A receptors are induced to accumulate cAMP by forskolin, pardoprunox functions as a full 5-HT1A receptor agonist with a low potency (pEC50 = 6.3).
Animal Protocol	0.03mg/kg; po Rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra pars compacta (SNpc)
References	[1]. In vitro characterization of SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone, monohydrochloride): a novel partial dopamine D2 and D3 receptor agonist and serotonin 5-HT1A receptor agonist. Synapse. 2006 Dec 15;60(8):599-608. [2]. An in vivo pharmacological evaluation of pardoprunox (SLV308)--a novel combined dopamine D(2)/D(3) receptor partial agonist and 5-HT(1A) receptor agonist with efficacy in experimental models of Parkinson's disease. Eur Neuropsychopharmacol . 2010 Aug;20(8):582-93.

Solubility Data

Solubility (In Vitro)

DMSO: 30~150 mg/mL (111.2~556.1 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 7.5 mg/mL (27.81 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 75.0 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: ≥ 7.5 mg/mL (27.81 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 75.0 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 3: ≥ 7.5 mg/mL (27.81 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 75.0 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	3.7074 mL	18.5371 mL	37.0741 mL
	5 mM	0.7415 mL	3.7074 mL	7.4148 mL
	10 mM	0.3707 mL	1.8537 mL	3.7074 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.