GR103545 is a potent and specific kappa-opioid receptor (κ-OR) agonist. 11GR103545 is a radioactive tracer that can be used for in vivo imaging.

Physicochemical Properties

Molecular Formula	C23H29CL2N3O7
Molecular Weight	530.39826464653
Exact Mass	529.14
Elemental Analysis	C, 52.08; H, 5.51; Cl, 13.37; N, 7.92; O, 21.11
CAS #	126766-43-6
Related CAS #	126766-43-6 (fumarate); 126766-42-5
PubChem CID	9893214
Appearance	Solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	649
Defined Atom Stereocenter Count	1
SMILES	COC(=O)N1CCN([C@@H](C1)CN2CCCC2)C(=O)CC3=CC(=C(C=C3)Cl)Cl.C(=C/C(=O)O)\C(=O)O
InChi Key	ABTNETSDXZBJTE-WMQZXYHMSA-N
InChi Code	InChI=1S/C19H25Cl2N3O3.C4H4O4/c1-27-19(26)23-8-9-24(15(13-23)12-22-6-2-3-7-22)18(25)11-14-4-5-16(20)17(21)10-14;5-3(6)1-2-4(7)8/h4-5,10,15H,2-3,6-9,11-13H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t15-;/m1./s1
Chemical Name	(E)-but-2-enedioic acid;methyl (3R)-4-[2-(3,4-dichlorophenyl)acetyl]-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate
Synonyms	GR-103545 fumarate; GR 103545; GR-103545; GR103545
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	BRAF V600E ( IC50 = 8.2 nM ); BRAF ( IC50 = 19 nM ); CRAF ( IC50 = 56 nM ); MEK1 ( IC50 = 160 nM )
ln Vivo	This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. . They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. [1] Brain uptake of 11C-GR103545 was studied in baboons under control conditions and after blockade by naloxone (1 mg/kg intravenously). Uptake of the racemic 11C-GR89696 and of the inactive enantiomer (+)-11C-GR89696 was also evaluated. Regional total distribution volumes were derived using the arterial input function and a 2-tissue-compartment model.[2]
References	[1]. A series of novel, highly potent and selective agonists for the kappa-opioid receptor. Br J Pharmacol. 1990 Dec;101(4):944-8. [2]. 11C-GR103545, a radiotracer for imaging kappa-opioid receptors in vivo with PET: synthesis and evaluation in baboons. J Nucl Med. 2005 Mar;46(3):484-94.

Solubility Data

Solubility (In Vitro)

DMSO: 94~100 mg/mL (188.5~199.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.71 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 (4.71 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 3: ≥ 2.5 mg/mL (4.71 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. Solubility in Formulation 4: 5% DMSO+ 45% PEG300+ ddH2O: 1.0mg/ml (2.12mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8854 mL	9.4268 mL	18.8537 mL
	5 mM	0.3771 mL	1.8854 mL	3.7707 mL
	10 mM	0.1885 mL	0.9427 mL	1.8854 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.