ORL1 antagonist 1 is an opioid receptor 1 (ORL1) antagonist (inhibitor) with IC50 of 61 nM.

Physicochemical Properties

Molecular Formula	C20H22CLN5
Molecular Weight	367.875182628632
Exact Mass	367.156
CAS #	1174985-59-1
PubChem CID	44143417
Appearance	Typically exists as solid at room temperature
LogP	3.4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	444
Defined Atom Stereocenter Count	0
InChi Key	GZENXSQONSXYLR-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H22ClN5/c1-14-18(13-24-16-7-2-3-8-16)25-26(20-17(21)9-5-11-23-20)19(14)15-6-4-10-22-12-15/h4-6,9-12,16,24H,2-3,7-8,13H2,1H3
Chemical Name	N-[[1-(3-chloropyridin-2-yl)-4-methyl-5-pyridin-3-ylpyrazol-3-yl]methyl]cyclopentanamine
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
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	ORL1 antagonist 1 is an antagonist of the opioid receptor-like 1 (ORL1). Its binding affinity (IC50) for the human ORL1 receptor is 350 nM. It also shows binding affinity for the human ether-a-go-go related gene (hERG) potassium channel.[1]
ln Vitro	ORL1 antagonist 1 is compound 17 [1]. ORL1 antagonist 1 showed sub-micromolar ORL1 binding affinity and antagonistic activity. It also possessed potent hERG K+ channel binding affinity.[1]
Enzyme Assay	The binding affinity of compounds for the human ORL1 receptor was determined by measuring their ability to displace the binding of 125I-labeled Tyr14-Nociceptin/Orphanin FQ (125I-Tyr14-NC/OFQ) to membrane fractions of CHO cells expressing the ORL1 receptor.[1] The agonist or antagonist activities of compounds were measured using the 35S-GTPγS binding method with membrane fractions of CHO cells expressing the ORL1 receptor.[1] The binding affinity for the hERG potassium channel was measured by displacement of 35S-radiolabeled MK-499 in membranes derived from HEK293 cells stably transfected with the hERG gene and expressing the IKr channel protein.[1]
References	[1]. Discovery of novel arylpyrazole series as potent and selective opioid receptor-like 1 (ORL1) antagonists. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3627-31.
Additional Infomation	ORL1 antagonist 1 is an arylpyrazole derivative identified from screening a compound library. It served as the lead compound for structure-activity relationship (SAR) studies aimed at improving ORL1 potency and selectivity while reducing hERG channel affinity.[1]

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7183 mL	13.5914 mL	27.1828 mL
	5 mM	0.5437 mL	2.7183 mL	5.4366 mL
	10 mM	0.2718 mL	1.3591 mL	2.7183 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.