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Related Concept Videos

Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

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Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
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Drugs that Stabilize Microtubules01:15

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Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
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Destabilization of Microtubules01:45

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The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
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Microtubule Associated Proteins (MAPs)01:42

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Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
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Microtubule Instability02:17

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Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
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Microtubules01:35

Microtubules

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There are three types of cytoskeletal structures in eukaryotic cells—microfilaments, intermediate filaments, and microtubules. With a diameter of about 25 nm, microtubules are the thickest of these fibers. Microtubules carry out a variety of functions that include cell structure and support, transport of organelles, cell motility (movement), and the separation of chromosomes during cell division.
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Recent Progress on Microtubule Degradation Agents.

Chufeng Zhang1, Min Zhao2, Guan Wang1

  • 1Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, China.

Journal of Medicinal Chemistry
|September 25, 2023
PubMed
Summary
This summary is machine-generated.

Targeted protein degradation (TPD) offers a novel way to combat drug resistance by degrading disease proteins. Microtubule degradation agents (MDgAs) represent a new class of TPD, overcoming limitations of traditional microtubule-targeting agents.

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Area of Science:

  • Molecular Biology
  • Drug Discovery
  • Oncology

Background:

  • Targeted protein degradation (TPD) utilizes cellular machinery for specific protein knockdown, offering advantages over traditional therapies by degrading entire proteins.
  • Microtubule-targeting agents (MTAs) are established chemotherapy drugs, but clinical use is limited by drug resistance, hypersensitivity, and toxicity.
  • Microtubule degradation agents (MDgAs) represent a new TPD approach distinct from MTAs, designed to overcome existing resistance mechanisms.

Purpose of the Study:

  • To summarize the development and mechanisms of Microtubule Degradation Agents (MDgAs).
  • To explore the potential of MDgAs in overcoming limitations of traditional Microtubule-Targeting Agents (MTAs).
  • To discuss opportunities and challenges in the field of tubulin-targeted drug discovery via TPD.

Main Methods:

  • Review of existing literature on Targeted Protein Degradation (TPD) technologies.
  • Analysis of the mechanisms of action for Microtubule Degradation Agents (MDgAs).
  • Comparison of MDgA mechanisms with traditional Microtubule-Targeting Agents (MTAs).

Main Results:

  • MDgAs degrade target proteins via TPD, offering a different mechanism than MTAs.
  • MDgAs show potential to overcome drug resistance and reduce toxicities associated with conventional MTAs.
  • The development of MDgAs expands the scope of TPD for novel tubulin-targeted therapies.

Conclusions:

  • MDgAs represent a promising advancement in cancer therapy by leveraging targeted protein degradation.
  • This approach offers a viable strategy to overcome resistance and toxicity issues inherent in current microtubule-targeting drugs.
  • Further research into MDgAs holds significant potential for developing next-generation anti-cancer therapeutics.