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Target-Specific Neosubstrate
- Molecular classification
- Protein, Varies by compound
01
Overview
A target-specific neosubstrate is a protein that is not normally targeted for degradation by an E3 ubiquitin ligase but becomes a target when recruited by a small molecule such as a molecular glue or PROTAC. The identity of the neosubstrate depends on the specific compound used. These compounds induce proximity between an E3 ligase (typically CRBN) and the neosubstrate, leading to ubiquitination and degradation. Examples include IKZF1, IKZF3, GSPT1, CK1α, and SALL4. The degradation of these proteins can underlie both therapeutic efficacy and adverse effects.
- Other names
- Compound-induced neosubstrateMolecular glue targetPROTAC target
02
Mechanism of action
E3 ubiquitin ligase recruitment; induced proximity; ubiquitination and proteasomal degradation
03
Biological functions
Varies by proteinProtein degradationRegulation of protein function
04
Disease associations
CancerTeratogenicityVaries by protein
05
Safety considerations
Off-target effectsToxicityUnintended degradation of essential proteins
06
Interacting drugs
Molecular glues
6 more in the full profile.
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