Selective CTPS1 Inhibitors for Reduced Off-Target Effects
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies targeting nucleotide biosynthesis lack specificity for CTP synthase 1 (CTPS1), which is crucial for immune cell proliferation and proliferation-related diseases, leading to potential off-target effects and reduced therapeutic index.
Innovation Solution
Development of compounds that act as selective inhibitors of CTPS1, reducing its activity to treat conditions associated with immune dysfunction, autoimmune diseases, and hematological cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broader nucleotide biosynthesis-targeting therapies are used, then therapeutic benefit is achieved, but specificity for CTPS1 is reduced leading to off-target effects
Solution Approach 1:
The invention segments the nucleotide biosynthesis pathway by developing compounds that specifically target CTPS1 rather than inhibiting multiple enzymes in the pathway. This selective targeting approach isolates the therapeutic action to CTPS1 inhibition, reducing off-target effects while maintaining therapeutic benefit for immune-related diseases
Solution Approach 2:
The patent applies local quality by designing compounds with specific molecular structures (formula I with defined substituents R1, Ring A, Ring B, Ring C, L, m, n, p, q) that confer selectivity for CTPS1. The localized chemical modifications at specific positions create high affinity and specificity for the CTPS1 active site, ensuring targeted inhibition without affecting other nucleotide biosynthesis enzymes
2Object-generated harmful factors
If CTPS1 activity is inhibited, then immune cell proliferation is reduced treating autoimmune diseases, but CTPS1 is crucial for immune cell proliferation requiring balanced inhibition
Solution Approach 1:
The invention applies partial action by using CTPS1 inhibitors at doses and regimens that achieve sufficient inhibition to treat autoimmune diseases and immune proliferation disorders, while avoiding complete or excessive inhibition that would cause severe immunodeficiency. The compounds enable controlled, partial inhibition tailored to disease severity
Solution Approach 2:
The patent employs parameter changes by modifying molecular parameters of the inhibitor compounds (substituent groups, ring structures, linkers) to fine-tune the potency and selectivity of CTPS1 inhibition. This allows optimization of the therapeutic window to achieve adequate immune suppression for disease treatment while preserving essential immune functions
Data Source
AI summary
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CPTS1, and the treatment of CPTS1-mediated disorders.