Source 1review2022ACS Pharmacology & Translational Science
Toolkit/proteolysis targeting chimera
proteolysis targeting chimera
Also known as: PROTAC, PROTACs
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The development of proteolysis targeting chimeras (PROTACs) that trigger degradation of the target proteins provides a conceptually novel approach to address drug targets that remained previously elusive.
Usefulness & Problems
Why this is useful
PROTACs are described as molecules that trigger degradation of target proteins. The review frames them as a novel modality for targets that remain intractable to conventional small-molecule modulation.; targeted protein degradation; addressing drug targets that are difficult to modulate with small molecules
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PROTACs are described as molecules that trigger degradation of target proteins. The review frames them as a novel modality for targets that remain intractable to conventional small-molecule modulation.
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targeted protein degradation
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addressing drug targets that are difficult to modulate with small molecules
Problem solved
They offer a way to address drug targets that were previously elusive for small-molecule modulation. The review centers on improving how effectively and selectively they do this.; providing a route to act on previously elusive drug targets
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They offer a way to address drug targets that were previously elusive for small-molecule modulation. The review centers on improving how effectively and selectively they do this.
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providing a route to act on previously elusive drug targets
Problem links
providing a route to act on previously elusive drug targets
LiteratureThey offer a way to address drug targets that were previously elusive for small-molecule modulation. The review centers on improving how effectively and selectively they do this.
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They offer a way to address drug targets that were previously elusive for small-molecule modulation. The review centers on improving how effectively and selectively they do this.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
No technique tags yet.
Target processes
degradationInput: Chemical
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: regulator
requires design strategies that improve effectiveness and selectivity; must balance efficiency, selectivity, drug-likeness, and safety
The abstract states that efficient, tissue- and cell-selective PROTACs with good drug-likeness and favorable safety profiles are still difficult to identify.; identification of efficient PROTAC molecules remains a main challenge; tissue- and cell-selective PROTAC design remains challenging; good drug-likeness and favorable safety profiles remain challenging
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
A main challenge in PROTAC development is identifying efficient, tissue- and cell-selective molecules with good drug-likeness and favorable safety profiles.
PROTACs provide a conceptually novel approach for addressing drug targets that remain intractable for small-molecule modulation.
Approval Evidence
1 source2 linked approval claimsfirst-pass slug proteolysis-targeting-chimera
The development of proteolysis targeting chimeras (PROTACs) that trigger degradation of the target proteins provides a conceptually novel approach to address drug targets that remained previously elusive.
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development challengesupports
A main challenge in PROTAC development is identifying efficient, tissue- and cell-selective molecules with good drug-likeness and favorable safety profiles.
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modality positioningsupports
PROTACs provide a conceptually novel approach for addressing drug targets that remain intractable for small-molecule modulation.
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Comparisons
Source-stated alternatives
The abstract contrasts PROTACs with small-molecule modulation, noting that some targets remain intractable for conventional small molecules.
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The abstract contrasts PROTACs with small-molecule modulation, noting that some targets remain intractable for conventional small molecules.
Source-backed strengths
conceptually novel approach based on triggering target protein degradation
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conceptually novel approach based on triggering target protein degradation
Compared with autophagy-targeting chimeras
proteolysis targeting chimera and autophagy-targeting chimeras address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: chemical
Compared with bacterial degrons
proteolysis targeting chimera and bacterial degrons address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: chemical
Compared with PROTAC
proteolysis targeting chimera and PROTAC address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: chemical
Ranked Citations
- 1.