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Related Concept Videos

Microtubule Instability02:17

Microtubule Instability

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 assembly and...
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

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...
Destabilization of Microtubules01:45

Destabilization of Microtubules

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...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

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...
Microtubule Instability02:17

Microtubule Instability

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 assembly and...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

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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Related Experiment Video

Updated: Jul 24, 2026

Spatiotemporal Subcellular Manipulation of the Microtubule Cytoskeleton in the Living Preimplantation Mouse Embryo using Photostatins
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Spatiotemporal Subcellular Manipulation of the Microtubule Cytoskeleton in the Living Preimplantation Mouse Embryo using Photostatins

Published on: November 30, 2021

Microtubule-stabilizing agents based on designed laulimalide analogues.

Susan L Mooberry1, Deborah A Randall-Hlubek, Rachel M Leal

  • 1Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, 7620 Northwest Loop 410, San Antonio, TX 78227, USA. smooberry@sfbr.org

Proceedings of the National Academy of Sciences of the United States of America
|May 27, 2004
PubMed
Summary

New laulimalide analogues, designed for improved stability, effectively inhibit cancer cell proliferation. Some analogues retain laulimalide's unique microtubule-stabilizing activity and show promise against drug-resistant cancer cells.

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Spatiotemporal Subcellular Manipulation of the Microtubule Cytoskeleton in the Living Preimplantation Mouse Embryo using Photostatins
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Area of Science:

  • Marine natural products chemistry
  • Medicinal chemistry
  • Cancer biology

Background:

  • Laulimalide, a marine sponge-derived compound, is a potent microtubule-stabilizing agent.
  • It exhibits unique activity against paclitaxel-resistant cancer cells but suffers from chemical instability.
  • Developing stable analogues is crucial for therapeutic applications.

Purpose of the Study:

  • To design and synthesize novel laulimalide analogues with enhanced chemical stability.
  • To evaluate the biological activities and mechanisms of action of these analogues.
  • To assess their efficacy against cancer cell proliferation, including drug-resistant lines.

Main Methods:

  • Chemical synthesis of five laulimalide analogues.
  • In vitro evaluation of cytotoxicity and antiproliferative effects (IC50 determination).
  • Cellular assays to observe effects on microtubule dynamics, mitosis, and apoptosis.

Main Results:

  • All synthesized analogues inhibited cancer cell proliferation, with potencies ranging from 0.12-16.5 microM.
  • Two analogues, C(16)-C(17)-des-epoxy laulimalide and C(20)-methoxy laulimalide, showed mechanisms identical to laulimalide.
  • Analogues demonstrated effectiveness against paclitaxel- and epothilone-resistant cell lines.

Conclusions:

  • Chemically stabilized laulimalide analogues retain significant anticancer activity.
  • Specific modifications can fine-tune potency and mechanism of action.
  • These analogues represent promising leads for developing new chemotherapeutics, especially for resistant cancers.