Delving into the Latest Updates on LY-290324 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CysLT

Mechanism

CysLT antagonists(Cysteinyl leukotriene receptor antagonists)

Therapeutic Areas

Immune System DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Asthma

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Eli Lilly & Co.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

This study describes the evaluation of LY290324 as a leukotriene D4 (LTD4) receptor antagonist in guinea-pigs. In vitro, LY290324 was a potent and persistent antagonist of the contractile responses to LTD4 and LTE4 with pA2 values of 9.1 +/- 0.2 and 8.9 +/- 0.17 respectively. The antagonism appeared competitive and selective for LTD4/E4, as LY290324 (10(-6) M) had no effects on contraction elicited by LTC4, prostaglandin F2 alpha (PGF2 alpha), histamine and acetylcholine. In vivo the compound was highly effective in a dose-dependent manner by the intravenous, oral and inhaled routes in preventing LTD4-induced bronchospasm. Administered i.v. LY290324 prevented the development (ED50 = 3.4 micrograms/kg) of an LTD4-induced bronchospasm and readily reversed an established bronchospasm, but failed to prevent the bronchospasm to either histamine or platelet activating factor (PAF). Oral studies demonstrated efficacy for at least 12 h. Administered orally 6 h previously, LY290324 reduced LTC4, LTD4 and LTE4-induced bronchospasm with ED50s of 0.3, 0.28 and 0.37 mg/kg respectively. Relatively low inhaled levels (2 micrograms/kg) also significantly reduced (72.5%, P < 0.001) LTD4-induced bronchospasm. Finally the compound administered orally was effective in reducing antigen-induced bronchospasm in immunologically sensitised animals.

100 Deals associated with LY-290324

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