Tel: 732-484-9848
Fax: 888-484-5008
Email: sales@chemscene.com
   
Buliding blocks
Intermediates
Bioactive molecules
Product Pathways
All Targets
Anti-infection
Antibody-drug conjugate....
Apoptosis
Biochemical Reagent
Cell Cycle/DNA Damage
GPCR/G protein
Immunology/Inflammation
JAK/STAT Signaling
MAPK/ERK Pathway
Membrane Transporter/Io....
Metabolism/Protease
Microbiology
Neuronal Signaling
NF-KB
Others
PI3K/Akt/mTOR
Protein Tyrosine Kinase....
TGF-beta/Smad
Vitamin D Related
Wnt/Hedgehog/Notch
Research Area
Cancer
Cardiovascular Disease
Endocrinology
Infection
Metabolic Disease
Neurological Disease
Others
Inflammation/Immunology
Product Type
All Products
New Products
Featured Products
Home   »   Product Pathways  »  Opioid Receptor  »  ADL-5859

Products are for research use only. Not for human use. We do not sell to patients.


CS-0428 ADL-5859


(ADL5859; ADL 5859)
Structure Price and Availability of    ADL-5859
United States
Size Price Stock
5mg $132 In-stock Inquiry
1g Get quote
5g Get quote
>10g Get quote
 Distributor In Japan:  フナコシ株式会社 www.funakoshi.co.jp    
電話番号:81-3-5684-1620    FAX番号:81-3-5684-1775
Inquiry for price and availability only. Please place your order via our email or fax.
Contact us for competitive discounts on bulk quantities .
  • Data Sheet
  • Introduction
  • References
  • Related Products

ADL-5859  M.Wt: 428.96
ADL-5859  Formula: C24H29ClN2O3
ADL-5859  Solubility: DMSO ≥84mg/mL Water ≥10mg/mL Ethanol ≥0.8mg/mL
ADL-5859  Purity: >98%
ADL-5859  Storage:  Please store the product under the recommended conditions in the Certificate of Analysis.
CAS: 850173-95-4

View current batch:

ADL-5859 (ADL5859) is an δ-opioid receptor agonist (Ki=0.84 nM, EC50=20 nM). ADL-5859 (ADL5859) is an agonist agent that selectively stimulates the δ-opioid receptor with potential application in a wide range of inflammatory, neuropathic and acute pain conditions. In addition, Delta agonists are thought to modulate other biological processes that may manifest themselves in disease states or conditions such as overactive bladder and depression.ADL-5859 (ADL5859) is useful for inflammatory, neuropathic and acute pain conditions.

1 . Le Bourdonnec B, Windh RT, Ajello CW, Leister LK, Gu M, Chu GH, Tuthill PA, Barker WM, Koblish M, Wiant DD, Graczyk TM, Belanger S, Cassel JA, Feschenko MS, Brogdon BL, Smith SA, Christ DD, Derelanko MJ, Kutz S, Little PJ, DeHaven RN, DeHaven-Hudkins DL, Dolle RE.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. Epub 2008 Sep 13.
Abstract
Selective delta opioid receptor agonists are promising potential therapeutic agents for the treatment of various types of pain conditions. A spirocyclic derivative was identified as a promising hit through screening. Subsequent lead optimization identified compound 20 (ADL5859) as a potent, selective, and orally bioavailable delta agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.

2 . Le Bourdonnec B, Windh RT, Leister LK, Zhou QJ, Ajello CW, Gu M, Chu GH, Tuthill PA, Barker WM, Koblish M, Wiant DD, Graczyk TM, Belanger S, Cassel JA, Feschenko MS, Brogdon BL, Smith SA, Derelanko MJ, Kutz S, Little PJ, DeHaven RN, DeHaven-Hudkins DL, Dolle RE.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.
Abstract
Selective, nonpeptidic delta opioid receptor agonists have been the subject of great interest as potential novel analgesic agents. The discoveries of BW373U86 (1) and SNC80 (2) contributed to the rapid expansion of research in this field. However, poor drug-like properties and low therapeutic indices have prevented clinical evaluation of these agents. Doses of 1 and 2 similar to those required for analgesic activity produce convulsions in rodents and nonhuman primates. Recently, we described a novel series of potent, selective, and orally bioavailable delta opioid receptor agonists. The lead derivative, ADL5859 (4), is currently in phase II proof-of-concept studies for the management of pain. Further structure activity relationship exploration has led to the discovery of ADL5747 (36), which is approximately 50-fold more potent than 4 in an animal model of inflammatory pain. On the basis of its favorable efficacy, safety, and pharmacokinetic profile, 36 was selected as a clinical candidate for the treatment of pain.

3 . Nozaki C, Le Bourdonnec B, Reiss D, Windh RT, Little PJ, Dolle RE, Kieffer BL, Gavériaux-Ruff C.δ-Opioid Mechanisms for ADL5747 and ADL5859 Effects in Mice: Analgesia, Locomotion, and Receptor Internalization.J Pharmacol Exp Ther. 2012 Sep;342(3):799-807. Epub 2012 Jun 13.
Abstract
N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl) benzamide (ADL5859) and N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5747) are novel δ-opioid agonists that show good oral bioavailability and analgesic and antidepressive effects in the rat and represent potential drugs for chronic pain treatment. Here, we used genetic approaches to investigate molecular mechanisms underlying their analgesic effects in the mouse. We tested analgesic effects of ADL5859 and ADL5747 in mice by using mechanical sensitivity measures in both complete Freund's adjuvant and sciatic nerve ligation pain models. We examined their analgesic effects in δ-opioid receptor constitutive knockout (KO) mice and mice with a conditional deletion of δ-receptor in peripheral voltage-gated sodium channel (Nav)1.8-expressing neurons (cKO mice). Both ADL5859 and ADL5747, and the prototypical δ agonist 4-[(R)-[(2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl]-(3-methoxyphenyl)methyl]-N,N-diethyl-benzamide (SNC80) as a control, significantly reduced inflammatory and neuropathic pain. The antiallodynic effects of all three δ-opioid agonists were abolished in constitutive δ-receptor KO mice and strongly diminished in δ-receptor cKO mice. We also measured two other well described effects of δ agonists, increase in locomotor activity and agonist-induced receptor internalization by using knock-in mice expressing enhanced green fluorescence protein-tagged δ receptors. In contrast to SNC80, ADL5859 and ADL5747 did not induce either hyperlocomotion or receptor internalization in vivo. In conclusion, both ADL5859 and ADL5747 showed efficient pain-reducing properties in the two models of chronic pain. Their effects were mediated by δ-opioid receptors, with a main contribution of receptors expressed on peripheral Nav1.8-positive neurons. The lack of in vivo receptor internalization and locomotor activation, typically induced by SNC80, suggests agonist-biased activity at the receptor for the two drugs.

4 . Le Bourdonnec B et al. 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.
Abstract
Selective delta opioid receptor agonists are promising potential therapeutic agents for the treatment of various types of pain conditions. A spirocyclic derivative was identified as a promising hit through screening. Subsequent lead optimization identified compound 20 (ADL5859) as a potent, selective, and orally bioavailable delta agonist. Compound 20 was selected as a clinical candidate for the treatment of pain.

Opioid Receptor  |   Opioid Receptor  |  
Keywords: buy ADL-5859 | ADL-5859 Supplier | purchase ADL-5859 | ADL-5859 cost | ADL-5859 manufacturer | order ADL-5859 | ADL-5859 distributor | ADL-5859 structure,chemscene
buy 850173-95-4 | 850173-95-4 Supplier | purchase 850173-95-4 | 850173-95-4 cost | 850173-95-4 manufacturer | order 850173-95-4 | 850173-95-4 distributor | 850173-95-4 structure,chemscene


CHEMSCENE, LLC
Tel: 732-484-9848
Fax: 888-484-5008
Email:  sales@chemscene.com
Address: 11 Deer Park Drive, Suite 102D Monmouth Junction, NJ 08852.
Products are for research use only. Not for human use. We do not sell to patients. Sitemap | Inhibitor © Copyright 2012. All Rights Reserved.