Delving into the Latest Updates on RWJ-68023 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

GPR38

Mechanism

GPR38 antagonists(Motilin receptor antagonists)

Therapeutic Areas

Digestive System DisordersOther Diseases

Active Indication-

Inactive Indication

DyspepsiaIrritable Bowel Syndrome

Originator Organization

Johnson & Johnson

Active Organization-

Inactive Organization

Johnson & Johnson

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC34H37Cl3N4O4

InChIKeyDPBURRXPRULCQN-XIFFEERXSA-N

CAS Registry223442-22-6

A first-in-class non-peptide antagonist of the motilin receptor was identified through electronic screening of our corporate database against a 3D pharmacophore. The pharmacophore was developed from the motilin 22 residue endogenous peptide using NMR structural data, principles of peptide folding, and peptide structure activity relationships. The NMR data supported helical content within the peptide, and both the hydrophobic staple and N-capping box motifs were identified in the motilin sequence. The conformational features of these motifs were imposed on the peptide structure, providing a constrained conformer as a starting point for database searching. A trisubstituted cyclopentene lead was identified directly from the electronic search. Compounds in this series inhibit the binding of 125I-motilin to human antral smooth muscle membrane and antagonize motilin-induced intracellular calcium mobilization in cells expressing the human motilin receptor. A potent compound developed through optimization, RWJ 68023, is active in binding and cell-based functional assays and is also effective in inhibiting motilin-induced contractility in segments of rabbit duodenum. This orally active compound is currently undergoing clinical evaluation for the treatment of gastrointestinal disorders associated with altered motility.

100 Deals associated with RWJ-68023

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