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Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)01:20

¹³C NMR: Distortionless Enhancement by Polarization Transfer (DEPT)

When proton-coupled carbon-13 spectra are simplified by a broadband proton decoupling technique, structural information about the coupled protons is lost. Distortionless enhancement by polarization transfer (DEPT) is a technique that provides information on the number of hydrogens attached to each carbon in a molecule. While the DEPT experiment utilizes complex pulse sequences, the pulse delay and flip angle are specifically manipulated. The resulting signals have different phases depending on...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Optimizing Chromatographic Separations01:15

Optimizing Chromatographic Separations

Optimizing chromatographic separations is crucial for obtaining clean separations in a minimum amount of time. Optimization is required for several factors, including kinetic effects related to band broadening, plate height, capacity factor, and separation factor.
Band broadening refers to spreading solute bands as they travel through the column. This broadening can impact resolution. Plate height (H) represents the length required for one theoretical plate. A lower plate height corresponds to...
Optimization Problems01:26

Optimization Problems

Optimization problems often involve identifying maximum or minimum values under specific constraints. A well-known example is determining the longest horizontal pipe that can be moved around a right-angled corner, where a 3-meter-wide hallway meets a 2-meter-wide hallway. This scenario, common in architectural design and industrial transport, can be understood conceptually through geometric and trigonometric reasoning.To visualize the problem, consider the pipe as a straight line that touches...
Methods of Medium Optimization01:28

Methods of Medium Optimization

Optimizing growth media enhances microbial proliferation and maximizes product yield. Statistical experimental design methodologies provide structured and reproducible approaches, offering progressively higher levels of robustness and efficiency.The One-Factor-at-a-Time (OFAT) MethodThe One-Factor-at-a-Time (OFAT) method involves adjusting a single variable while keeping all others constant. However, it cannot detect interactions between variables, often leading to suboptimal outcomes when...

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Related Experiment Video

Updated: Jun 12, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Property-based optimisation of PROTACs.

James S Scott1, Iacovos N Michaelides2, Markus Schade1

  • 1Oncology R&D, AstraZeneca 1 Francis Crick Avenue Cambridge CB2 0AA UK jamie.scott@astrazeneca.com.

RSC Medicinal Chemistry
|November 18, 2024
PubMed
Summary
This summary is machine-generated.

Proteolysis-targeting chimeras (PROTACs) offer a novel therapeutic strategy for targeted protein degradation. This review analyzes clinical-stage PROTACs, focusing on physicochemical properties and challenges in achieving oral bioavailability for drug discovery.

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Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Pharmacology

Background:

  • PROTACs represent a groundbreaking therapeutic modality enabling targeted protein degradation.
  • This approach hijacks the cell's natural ubiquitin-proteasome system to eliminate disease-causing proteins.

Discussion:

  • The article critically evaluates current clinical-stage PROTACs, emphasizing their physicochemical attributes.
  • It delves into the intricate optimization of PROTAC components and the inherent challenges in developing orally bioavailable therapeutics.
  • Key difficulties in achieving oral bioavailability for PROTACs are highlighted, offering insights for medicinal chemists.

Key Insights:

  • Physicochemical properties are crucial for the efficacy and developability of PROTACs.
  • Optimizing PROTAC design involves balancing target engagement, degradation efficiency, and pharmacokinetic profiles.
  • Oral bioavailability remains a significant hurdle in advancing PROTAC therapeutics.

Outlook:

  • Continued innovation in PROTAC design is expected to overcome current limitations.
  • Further research into novel delivery strategies may enhance oral bioavailability.
  • PROTACs hold immense promise for future drug discovery and targeted therapies.