Delving into the Latest Updates on LPK-26 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

κ opioid receptor

Mechanism

κ opioid receptor agonists(Kappa opioid receptor agonists)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Pain

Originator Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

Active Organization-

Inactive Organization

Shanghai Institute of Materia Medica Chinese Academy of Sci

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC18H25Cl3N2O

InChIKeyWOOCHAFXTYNYQE-UNTBIKODSA-N

CAS Registry492451-07-7

Analgesics such as morphine cause many side effects including addiction, but kappa-opioid receptor agonist can produce antinociception without morphine-like side effects. With the aim of developing new and potent analgesics with lower abuse potential, we studied the antinociceptive and physical dependent properties of a derivate of ICI-199441, an analogue of (-)U50,488H, named (2-(3,4-dichloro)-phenyl)-N-methyl-N-[(1S)-1-(2-isopropyl)-2-(1-(3-pyrrolinyl))ethyl] acetamides (LPK-26). LPK-26 showed a high affinity to kappa-opioid receptor with the Ki value of 0.64 nM and the low affinities to micro-opioid receptor and delta-opioid receptor with the Ki values of 1170 nM and >10,000 nM, respectively. It stimulated [(35)S]GTPgammaS binding to G-proteins with an EC50 value of 0.0094 nM. In vivo, LPK-26 was more potent than (-)U50,488H and morphine in analgesia, with the ED50 values of 0.049 mg/kg and 0.0084 mg/kg in hot plat and acetic acid writhing tests, respectively. Moreover, LPK-26 failed to induce physical dependence, but it could suppress naloxone-precipitated jumping in mice when given simultaneously with morphine. Taken together, our results show that LPK-26 is a novel selective kappa-opioid receptor agonist with highly potent antinociception effects and low physical dependence potential. It may be valuable for the development of analgesic and drug that can be used to reduce morphine-induced physical dependence.

100 Deals associated with LPK-26

Login to view more data