ADL5859 HCl (ADL 5859; ADL-5859), the hydrochloride salt of ADL5859, is a potent, orally bioavailable δ-opioid receptor agonist with important biological activity. It has a Ki of 0.8 nM for δ-opioid receptor activation. ADL5859 demonstrated selectivity towards alternative opioid receptors, including κ and μ.

Physicochemical Properties

Molecular Formula	C24H29CLN2O3
Molecular Weight	428.95
Exact Mass	428.186
Elemental Analysis	C, 67.20; H, 6.81; Cl, 8.26; N, 6.53; O, 11.19
CAS #	850173-95-4
Related CAS #	850305-06-5 (ADL 5859 free base)
PubChem CID	46931003
Appearance	White to off-white solid powder
LogP	4.951
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	601
Defined Atom Stereocenter Count	0
SMILES	Cl.O=C(N(CC)CC)C1C=CC(C2C3C(=CC=CC=3O)OC3(CCNCC3)C=2)=CC=1
InChi Key	ZFNLSWREIULTDO-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H28N2O3.ClH/c1-3-26(4-2)23(28)18-10-8-17(9-11-18)19-16-24(12-14-25-15-13-24)29-21-7-5-6-20(27)22(19)21;/h5-11,16,25,27H,3-4,12-15H2,1-2H3;1H
Chemical Name	N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide;hydrochloride
Synonyms	ADL5859 HCl; ADL-5859; ADL 5859; ADL5859 HCl
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	δ Opioid Receptor/DOR
ln Vitro	In vitro activity: ADL-5859 (0-10 μM) hydrochloride inhibits 32% and 37% of the activities of the ε and κ opioid receptors, respectively, and exhibits activities to the δ opioid receptor with a Ki and an EC50 value of 0.84 and 20 nM[1]. ADL-5859 (0-100 μM) hydrochloride shows inhibitory activity to the hERG channel with an IC50 value of 78 μM[1]. ADL-5859 (0-100 μM) hydrochloride inhibits the activity of the drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6) in vitro with an IC50 value of 43 μM[2].
ln Vivo	ADL-5859 (0.3–10 mg/kg; p.o. once) hydrochloride exhibits strong antidepressant-like effects and reverses hyperalgesia in rats with inflamed paws[1].
Animal Protocol	Suspended in 0.5% methyl cellulose solution or dissolved in 5% sorbitol; 10 mg/kg; oral or i.v. injection Male ICR (CD-1) subjected to nociceptin-induced allodynia test or hot plate test, and Male SD rats subjected to formalin-induced paw-licking response
References	[1]. Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859). J Med Chem. 2008 Oct 9;51(19):5893-6. [2]. Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) benzamide (ADL5747).J Med Chem. 2009 Sep 24;52(18):5685-702.

Solubility Data

Solubility (In Vitro)

DMSO: ~86 mg/mL (~200.5 mM) Water: ~5 mg/mL (~11.6 mM) Ethanol: ~1 mg/mL (~2.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.75 mg/mL (6.41 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 27.5 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: ≥ 2.75 mg/mL (6.41 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 27.5 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: 0.5% hydroxyethyl cellulose+0.1% Tween 80: 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3313 mL	11.6564 mL	23.3127 mL
	5 mM	0.4663 mL	2.3313 mL	4.6625 mL
	10 mM	0.2331 mL	1.1656 mL	2.3313 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.