(1R,2R)-2-PCCA HCl is a potent GPR88 receptor agonist (activator) with EC50 of 3 nM in non-cell systems and 603 nM in cellular systems.

Physicochemical Properties

Molecular Formula	C30H39CL2N3O
Molecular Weight	528.556165933609
Exact Mass	527.247
CAS #	1609563-71-4
Related CAS #	2-PCCA hydrochloride
PubChem CID	134128291
Appearance	Light yellow to khaki solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	10
Heavy Atom Count	36
Complexity	623
Defined Atom Stereocenter Count	4
SMILES	Cl.Cl.O=C([C@@H]1C[C@H]1C1C=CC=CN=1)N(C1C=CC(C2C=CC(CCC)=CC=2)=CC=1)C[C@H]([C@@H](C)CC)N
InChi Key	ZRMICUFWAJDIQJ-QUDNCWCRSA-N
InChi Code	InChI=1S/C30H37N3O.2ClH/c1-4-8-22-10-12-23(13-11-22)24-14-16-25(17-15-24)33(20-28(31)21(3)5-2)30(34)27-19-26(27)29-9-6-7-18-32-29;;/h6-7,9-18,21,26-28H,4-5,8,19-20,31H2,1-3H3;2*1H/t21-,26+,27+,28+;;/m0../s1
Chemical Name	(1R,2R)-N-[(2S,3S)-2-amino-3-methylpentyl]-N-[4-(4-propylphenyl)phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;dihydrochloride
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.
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	(1R, 2R)-2-PCCA hydrochloride (Example 3) has an EC50 of 3 nM in cell-free assays and 603 nM in cellular experiments, making it a strong GPR88 receptor agonist[1][2]. (1R, 2R)-2-PCCA hydrochloride suppresses the GPR88-mediated cAMP synthesis via the Gαi-coupled pathway, with an EC50 of 56 nM cAMP structure in HEK293 cells that express GloSensor-22F and the human GPR88 receptor [2].
ln Vitro	(1R, 2R)-2-PCCA hydrochloride (Example 3) has an EC50 of 3 nM in cell-free assays and 603 nM in cellular experiments, making it a strong GPR88 receptor agonist[1][2]. (1R, 2R)-2-PCCA hydrochloride suppresses the GPR88-mediated cAMP synthesis via the Gαi-coupled pathway, with an EC50 of 56 nM cAMP structure in HEK293 cells that express GloSensor-22F and the human GPR88 receptor [2]. In HEK293T cells transiently co-transfected with human GPR88 and a luminescent cAMP biosensor, (1R,2R)-2-PCCA (hydrochloride) inhibited isoproterenol-induced cAMP accumulation with an EC50 of 373 nM (pEC50 = 6.22). In HEK293 cells stably expressing the human GPR88 receptor and the GloSensor-22F cAMP construct, (1R,2R)-2-PCCA (hydrochloride) exhibited an EC50 of 603 nM (pEC50 = 6.22) for inhibiting isoproterenol-stimulated cAMP production. The compound did not induce calcium mobilization in HEK293T/GPR88 cells, indicating no Gαq-mediated response. [2]
Cell Assay	Transient Transfection cAMP Assay: HEK293T cells were transfected with human GPR88 cDNA and a pGloSensor-22F plasmid overnight. Cells were then plated in poly-L-lysine coated 384-well plates in medium containing 1% dialyzed fetal bovine serum. After incubation, assay buffer was added, followed by the test compound at serial dilutions for 15 minutes. Luciferin and isoproterenol (200 nM final) were added, and after another 15-minute incubation, luminescence was measured to assess cAMP levels. The assay specifically measured Gαi-activation by the compound's ability to inhibit isoproterenol-stimulated cAMP production. [2] Stable Cell Line cAMP Assay: HEK293 cells stably expressing human GPR88 and the pGloSensor-22F biosensor (GPR88-22F cells) were plated in 96-well assay plates overnight. The next day, culture medium was replaced with an equilibration medium containing GloSensor cAMP reagent for 2 hours at room temperature in the dark. Test compound dilutions were added, followed after 10 minutes by isoproterenol (100 nM final). After 30 minutes, luminescence was read. [2] Calcium Mobilization Assay (FLIPR): Calcium mobilization was measured in HEK293T/GPR88 cells using a fluorescent imaging plate reader (FLIPR) calcium assay. [2]
References	[1]. Modulators of G Protein-Coupled Receptor 88. US 20110251204 A1. [2]. Synthesis, pharmacological characterization, and structure-activity relationship studies of small molecular agonists for the orphan GPR88 receptor. ACS Chem Neurosci. 2014 Jul 16;5(7):576-87. [3]. Effect of Substitution on the Aniline Moiety of the GPR88 Agonist 2-PCCA: Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies. ACS Chem Neurosci. 2016 Oct 19;7(10):1418-1432.
Additional Infomation	(1R,2R)-2-PCCA hydrochloride is a diastereomer of 2-PCCA, and acts as a potent GPR88 receptor agonist, with an EC50 of 3 nM in cell-free assay, and 603 nM in cell assay. (1R,2R)-2-PCCA (hydrochloride) is the pure (1R,2R)-diastereomer of the racemic mixture compound 2-PCCA (1). It was synthesized via asymmetric cyclopropanation using a chiral porphyrin catalyst, followed by coupling and deprotection steps. Its chemical name is (1R,2R)-2-(pyridin-2-yl)cyclopropanecarboxylic acid [(2S,3S)-2-amino-3-methylpentyl]-(4'-propylbiphenyl-4-yl)amide dihydrochloride. It was approximately 5-fold more potent than its (1S,2S)-diastereomer (3) in the transient transfection cAMP assay. The study suggests GPR88 as a promising drug target for basal ganglia-associated disorders, and (1R,2R)-2-PCCA (hydrochloride) serves as a pharmacological tool for investigating GPR88 function. [2]

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~94.60 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.73 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 25.0 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: ≥ 2.5 mg/mL (4.73 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8919 mL	9.4597 mL	18.9193 mL
	5 mM	0.3784 mL	1.8919 mL	3.7839 mL
	10 mM	0.1892 mL	0.9460 mL	1.8919 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.