Delving into the Latest Updates on LY-210073 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

COX-2 x LTB4R

Mechanism

COX-2 inhibitors(Cyclooxygenase-2 inhibitors), LTB4R antagonists(Leukotriene B4 receptor antagonists)

Therapeutic Areas

Immune System DiseasesRespiratory DiseasesSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

ArthritisAsthmaInflammation

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

In an effort to develop increasingly potent and specific leukotriene B4 (LTB4) receptor antagonists, several xanthone dicarboxylic acids were synthesized and evaluated. Two separate synthetic routes were used to construct a xanthone nucleus containing a regiospecific orientation of each carboxylic acid pharmacophore. These compounds represent the major conformationally-restricted analogues of benzophenone dicarboxylic acids previously shown to antagonize the activation of human neutrophils by LTB4. The most potent agent was compound 32, which inhibited the specific binding of [3H]LTB4 to receptors on intact human neutrophils (IC50, 6.2 +/- 0.1 nM), LTB4-induced luminol-dependent chemiluminescence (IC50, 55 +/- 11 nM), aggregation (IC50, 133 +/- 42 nM), and chemotaxis (IC50, 899 +/- 176 nM). The compound was a poor antagonist of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced chemiluminescence (IC50, 1599 +/- 317 nM) and aggregation (IC50, 2166 +/- 432 nM), indicating specificity in the inhibition of LTB4-stimulated events. Compound 32 (LY210073), which was completely devoid of agonist activity, appears to be one of the strongest inhibitors of LTB4 receptor binding reported so far.

100 Deals associated with LY-210073

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