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Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides

During a screening performed by the National Cancer Institute in the 1960s, the terpenoid paclitaxel was discovered. Paclitaxel expanded the treatment options for breast, lung, prostate and ovarian cancer. Paclitaxel is only present in minute amounts in the bark of Taxia brevifolia. A sustainable su...

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Autor principal: Christensen, Søren Brøgger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457747/
https://www.ncbi.nlm.nih.gov/pubmed/36080414
http://dx.doi.org/10.3390/molecules27175648
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author Christensen, Søren Brøgger
author_facet Christensen, Søren Brøgger
author_sort Christensen, Søren Brøgger
collection PubMed
description During a screening performed by the National Cancer Institute in the 1960s, the terpenoid paclitaxel was discovered. Paclitaxel expanded the treatment options for breast, lung, prostate and ovarian cancer. Paclitaxel is only present in minute amounts in the bark of Taxia brevifolia. A sustainable supply was ensured with a culture developed from Taxus chinensis, or with semi-synthesis from other taxanes. Paclitaxel is marketed under the name Taxol. An intermediate from the semi-synthesis docetaxel is also used as a drug and marketed as Taxotere. O-Methylated docetaxel is used for treatment of some paclitaxel-resistant cancer forms as cabazitaxel. The solubility problems of paclitaxel have been overcome by formulation of a nanoparticle albumin-bound paclitaxel (NAB-paclitaxel, Abraxane). The mechanism of action is affinity towards microtubules, which prevents proliferation and consequently the drug would be expected primarily to be active towards cancer cells proliferating faster than benign cells. The activity against slowly growing tumors such as solid tumors suggests that other effects such as oncogenic signaling or cellular trafficking are involved. In addition to terpenoids, recently discovered microtubule-targeting polyketide macrolides and non-ribosomal peptides have been discovered and marketed as drugs. The revolutionary improvements for treatment of cancer diseases targeting microtubules have led to an intensive search for other compounds with the same target. Several polyketide macrolides, terpenoids and non-ribosomal peptides have been investigated and a few marketed.
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spelling pubmed-94577472022-09-09 Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides Christensen, Søren Brøgger Molecules Review During a screening performed by the National Cancer Institute in the 1960s, the terpenoid paclitaxel was discovered. Paclitaxel expanded the treatment options for breast, lung, prostate and ovarian cancer. Paclitaxel is only present in minute amounts in the bark of Taxia brevifolia. A sustainable supply was ensured with a culture developed from Taxus chinensis, or with semi-synthesis from other taxanes. Paclitaxel is marketed under the name Taxol. An intermediate from the semi-synthesis docetaxel is also used as a drug and marketed as Taxotere. O-Methylated docetaxel is used for treatment of some paclitaxel-resistant cancer forms as cabazitaxel. The solubility problems of paclitaxel have been overcome by formulation of a nanoparticle albumin-bound paclitaxel (NAB-paclitaxel, Abraxane). The mechanism of action is affinity towards microtubules, which prevents proliferation and consequently the drug would be expected primarily to be active towards cancer cells proliferating faster than benign cells. The activity against slowly growing tumors such as solid tumors suggests that other effects such as oncogenic signaling or cellular trafficking are involved. In addition to terpenoids, recently discovered microtubule-targeting polyketide macrolides and non-ribosomal peptides have been discovered and marketed as drugs. The revolutionary improvements for treatment of cancer diseases targeting microtubules have led to an intensive search for other compounds with the same target. Several polyketide macrolides, terpenoids and non-ribosomal peptides have been investigated and a few marketed. MDPI 2022-09-01 /pmc/articles/PMC9457747/ /pubmed/36080414 http://dx.doi.org/10.3390/molecules27175648 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Christensen, Søren Brøgger
Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides
title Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides
title_full Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides
title_fullStr Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides
title_full_unstemmed Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides
title_short Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides
title_sort drugs that changed society: microtubule-targeting agents belonging to taxanoids, macrolides and non-ribosomal peptides
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457747/
https://www.ncbi.nlm.nih.gov/pubmed/36080414
http://dx.doi.org/10.3390/molecules27175648
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