LPAR1 Antagonist Compounds for Selectivity and Metabolic Stability
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Solution Overview
Problem
There is a need for LPA receptor antagonists with desirable selectivity, potency, metabolic stability, or reduced detrimental effects for the treatment and/or prophylaxis of diseases associated with LPA receptors, such as cancer, fibrosis, inflammation, pain, and cardiovascular diseases.
Innovation Solution
Development of compounds that act as inhibitors of Lysophosphatidic Acid Receptor 1 (LPAR1) through specific binding, including pharmaceutical compositions and methods of administration to inhibit LPAR1 activity in subjects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing LPA receptor antagonists are used, then some therapeutic effect is achieved, but selectivity, potency, or metabolic stability is insufficient
Solution Approach 1:
The patent applies parameter changes by systematically modifying molecular parameters of the antagonist compounds, including substituting different fatty acid chains (saturated, unsaturated, cyclic), varying chain lengths (C16-C24), and adjusting structural configurations to optimize binding affinity and selectivity for LPAR1 over other LPA receptors, thereby achieving superior potency and selectivity while maintaining metabolic stability
2Adaptability or versatility
If LPA receptor antagonists are developed to treat multiple diseases, then versatility is improved, but complexity of compound design increases
Solution Approach 1:
The patent applies universality by designing a series of antagonist compounds with a common core structure that can bind to LPAR1 and mediate therapeutic effects across multiple disease states including fibrosis, cancer, inflammation, and cardiovascular diseases. The compounds are designed to be multi-functional, where modifications in the fatty acid side chains allow the same basic molecular framework to address different pathologies through LPA receptor modulation
Data Source
AI summary
The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH), interstitial lung disease (ILD), or chronic kidney disease (CKD).