Formula A Compounds Disrupt CD95 PLCγ1 Interaction
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Solution Overview
Problem
Current treatments lack effective compounds to reduce CD95-mediated cell motility, particularly in cancer and autoimmune inflammatory diseases such as systemic lupus erythematosus, where CD95-mediated cell motility contributes to disease progression and inflammation.
Innovation Solution
Development of novel compounds of formula (A) that specifically disrupt the CD95/PLCγ1 interaction without affecting the CD95/FADD interaction, thereby reducing CD95-mediated cell motility and alleviating clinical symptoms in lupus-prone mice.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used, then general disease management is maintained, but CD95-mediated cell motility cannot be effectively reduced
Solution Approach 1:
The patent employs small molecule compounds as intermediaries that specifically bind to the CD95/PLCγ1 interaction interface, disrupting the signaling complex formation. These compounds act as molecular mediators that selectively interfere with CD95-mediated motility pathways without affecting other CD95 functions, thereby resolving the contradiction between achieving specific therapeutic effect and maintaining general treatment safety
Solution Approach 2:
The invention changes the molecular parameters of existing CD95 interactors by developing small molecule compounds with specific binding properties to the CD95 death domain. These compounds modify the interaction parameters between CD95 and PLCγ1, enabling selective disruption of motility-inducing signaling while preserving apoptotic pathways, thus achieving reliable reduction of cell motility without compromising other disease management aspects
2Reliability
If compounds disrupting CD95/PLCγ1 interaction are developed, then CD95-mediated cell motility is reduced, but potential off-target effects on other CD95 interactions may occur
Solution Approach 1:
The patent applies local quality by designing compounds that target specifically the PLCγ1 binding site within the CD95 death domain, rather than the entire CD95 receptor. This localized targeting ensures that only the CD95/PLCγ1 interaction is disrupted, while other CD95 interactions such as CD95/FADD remain intact, thereby achieving reliable motility reduction without harmful off-target effects
Solution Approach 2:
The small molecule compounds serve as selective intermediaries that bind to the CD95/PLCγ1 interface with high specificity. These intermediary molecules are designed to fit precisely into the binding pocket formed by CD95 and PLCγ1, acting as molecular wedges that prevent their direct interaction without interfering with other protein-protein interactions involving CD95, thus resolving the contradiction between effective motility reduction and avoidance of harmful side effects
3Adaptability or versatility
If novel compounds are developed to treat autoimmune diseases and cancer, then therapeutic options are expanded, but complexity of treatment regimens increases
Solution Approach 1:
The patent develops compounds with universal applicability across multiple CD95-mediated pathologies including autoimmune diseases and cancer. The small molecule compounds target the conserved CD95/PLCγ1 interaction interface that is pathologically relevant in diverse diseases, enabling a single therapeutic agent to address multiple conditions, thereby expanding therapeutic options without proportionally increasing treatment regimen complexity
Solution Approach 2:
The invention changes the therapeutic parameter landscape by introducing small molecule compounds with optimized pharmacokinetic and pharmacodynamic properties. These compounds are designed to achieve therapeutic efficacy at manageable dosages with favorable safety profiles, making the expanded therapeutic options clinically feasible and not overly complex for implementation in diverse disease settings
Data Source
AI summary
The present invention relates the field of reducing CD95-mediated cell motility in a subject, in particular for their use in the reduction of CD-95 mediated cancer cell motility, the reduction of CD95-mediated lymphocyte motility and/or B cell maturation, or the treatment of B-cell tumors, in a subject. The inventors identified a novel family of compounds having the ability to disrupt CD95/PLCγ1 interaction and to neutralize the CD95-mediated calcium signaling pathway and cell migration in human peripheral blood lymphocytes (PBLs) and Th17 cells. Thus, the present invention relates to compounds of formula (A) as defined in the present text, to a pharmaceutical composition comprising said compounds in a pharmaceutically acceptable medium and to the use of these compounds and compositions as medicament, in particular for their use in the reduction or treatment of the above-mentioned pathologies, and in particular in the treatment of cancers and autoimmune inflammatory disease such as systemic lupus erythematosus, inflammatory condition and Th17-mediated disease.