Related Experiment Video
Updated: Jul 8, 2026
06:02
Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
Published on: February 20, 2017
Understanding tubulin/microtubule-taxane interactions: a quantitative structure-activity relationship study
Corwin Hansch1, Rajeshwar P Verma
1Department of Chemistry, Pomona College, 645 North College Avenue, Claremont, California 91711, USA.
Molecular Pharmaceutics
|January 4, 2008
Summary
This study explores taxane anticancer drug interactions with microtubules using quantitative structure-activity relationships (QSARs). Hydrophobicity and steric parameters are key to designing more effective taxane-based cancer therapies.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Computational Chemistry
Background:
- Paclitaxel and docetaxel are successful but limited microtubule-stabilizing anticancer agents.
- Limitations include side effects, drug resistance, and cross-resistance.
- New agents with improved activity are needed.
Purpose of the Study:
- To investigate the interaction of taxanes with the tubulin/microtubule system.
- To formulate quantitative structure-activity relationships (QSARs) for taxane derivatives.
- To guide the design of novel taxane-based anticancer drugs.
Main Methods:
- Formulation of six quantitative structure-activity relationships (QSARs).
- Analysis of hydrophobicity (pi) and steric parameters.
- Identification of parabolic correlations for activity prediction.
Main Results:
- Hydrophobicity (pi) and steric parameters significantly influence taxane activity.
- Parabolic correlations (eqs 3 and 7) with B5 and pi identify optimal parameter values.
- Eighteen novel compounds are proposed as potential synthetic targets with high biological activity.
Conclusions:
- QSAR models provide predictive guidance for designing new taxane anticancer drugs.
- Defined optimal hydrophobicity and steric parameters can lead to highly active compounds.
- Validated QSAR models support the rational design of next-generation taxane therapeutics.
Related Concept Videos
01:15Drugs 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...
01:45Destabilization 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...
01:10Drugs 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...
02:17Microtubule 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...
02:17Microtubule 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...
01:23Microtubule Formation
Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation of...