Delving into the Latest Updates on LY-264086 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

3-[4-[7-carboxy-3-[decyloxy]-9-oxo-9H-xanthene]]propanoic acid

+ [1]

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

AsthmaInflammationPsoriasis

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

A series of lipophilic benzophenone dicarboxylic acids have been shown to be inhibitors of the binding of LTB4 to its receptors on intact human neutrophils (Gapinski et al. (1990). Structure-activity relationships indicated that maximum activity was achieved when an acid group was attached at the meta position of each ring. In this report, the conformation of these inhibitors that binds best to the LTB4 receptor was determined. Inhibition concentration profiles of four rigid xanthone isomers that mimicked the four major conformational states of this type of benzophenone dicarboxylic acid were compared. LY264086, 3-[4-[7-carboxy-3-[decyloxy]-9-oxo-9H-xanthene]]propanoic acid, was the most potent inhibitor. The distance between the two carboxyl groups in this isomer was found to be 9.8 A, implying that the two acid binding sites on the receptor are separated by similar dimensions. Molecular modeling studies with low energy conformers of the xanthone isomers and LTB4 suggested a configuration of the agonist when it is bound to the receptor but did not exclude all other possibilities. These experiments further support the existence of two acid-binding sites on the human neutrophil LTB4 receptor.

100 Deals associated with LY-264086

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