Cereblon-Binding Small Molecules for Selective Tumor Cell Death
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Solution Overview
Problem
Current cereblon modulators, such as thalidomide and its derivatives, have adverse effects and limited efficacy in treating tumors and cancers, necessitating the development of novel compounds with improved substrate specificity for cereblon to enhance tumor cell death and minimize side effects.
Innovation Solution
Development of a novel low-molecular-weight compound with cereblon-binding activity, represented by specific chemical formulas, which can act as a cereblon ligand for treating tumors or cancers, including hematologic and solid cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thalidomide and its derivatives are used as cereblon modulators, then cereblon-binding activity is achieved, but adverse effects and limited efficacy occur
Solution Approach 1:
The patent modifies the chemical structure of existing cereblon modulators by changing molecular parameters such as substituting specific hydrogen atoms with fluorine atoms, adjusting ring structures, and modifying side chains. These parameter changes result in compounds with improved binding affinity to cereblon and enhanced therapeutic efficacy while reducing adverse effects associated with parent compounds like thalidomide
Solution Approach 2:
The invention creates composite molecular structures by combining specific heterocyclic rings (such as pyridine, pyrimidine, triazine) with various substituent groups and linkers. These composite structures exhibit synergistic effects that improve cereblon-binding activity and tumor cell death induction while minimizing off-target effects and toxicity
2Reliability
If current cereblon modulators are used, then some tumor cell death is induced, but substrate specificity for cereblon is limited
Solution Approach 1:
The patent introduces specific local structural features into the cereblon modulator molecules, such as particular heterocyclic ring systems with defined nitrogen atom positions and specific substituent placements. These local quality enhancements enable the compounds to selectively bind to cereblon with higher affinity and induce degradation of specific substrate proteins involved in tumor cell survival, thereby improving both tumor cell death induction and substrate specificity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compound exhibits superior binding affinity to cereblon, acting as a novel immunomodulator for effective treatment of tumors and cancers by inducing tumor cell death and modulating immune responses.
Implementation Method 1
binds to cereblon and modulates the substrate specificity of the CRL4 CRBN
Data Source
AI summary
The novel low-molecular-weight compound according to the present invention has a superior ability to bind to cereblon and thus can act as a novel immunomodulator for treating tumors or cancers.