Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell
Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate c...
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ftsyracuseuniv:oai:surface.syr.edu:che-1002 2023-05-15T15:52:52+02:00 Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell Di Pasqua, Anthony J. Goodisman, Jerry Dabrowiak, James C 2012-07-01T07:00:00Z application/pdf https://surface.syr.edu/che/42 https://surface.syr.edu/cgi/viewcontent.cgi?article=1002&context=che unknown SURFACE at Syracuse University https://surface.syr.edu/che/42 https://surface.syr.edu/cgi/viewcontent.cgi?article=1002&context=che http://creativecommons.org/licenses/by/3.0/ CC-BY Chemistry - Faculty Scholarship carboplatin self-association mechanism of action carbonate Chemistry text 2012 ftsyracuseuniv 2022-01-09T19:28:10Z Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate chloride leaving ligands. In water, carboplatin exists in a monomer-dimer equilibrium with an association constant of K (M -1) ≈ 391, a property that accounts for the long-term stability of its ready-to-use infusion solution. When administered in the clinic, carboplatin is believed to exert its biological effects by interacting with genomic DNA and proteins. The slower substitution kinetics of carboplatin, compared to cisplatin, has prompted investigators to focus on mechanisms by which the compound can be activated in vivo. Carbonate, which is in equilibrium with hydrogen carbonate, carbonic acid, and dissolved carbon dioxide, is ubiquitous in biological systems, and is found in high concentrations in the blood, the interstitial fluid, and the cytosol. Activation of carboplatin by carbonate, CO 3 2- (k 1 = 2.04 ± 0.81 × 10 -6 in 24 mM carbonate buffer, pH 7.5 at 37 °C), for example, leads to the formation of platinum species that are more cytotoxic than the parent drug. This short review focuses on the reason for the unusual stability of carboplatin in its aqueous ready-to-use infusion solution, describes the reactions of the drug with biologically common nucleophiles and summarizes the activation chemistry that make the drug more reactive toward substances present in the biological system. Text Carbonic acid Syracuse University Research Facility And Collaborative Environment (SUrface) |
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Syracuse University Research Facility And Collaborative Environment (SUrface) |
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carboplatin self-association mechanism of action carbonate Chemistry |
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carboplatin self-association mechanism of action carbonate Chemistry Di Pasqua, Anthony J. Goodisman, Jerry Dabrowiak, James C Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell |
topic_facet |
carboplatin self-association mechanism of action carbonate Chemistry |
description |
Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate chloride leaving ligands. In water, carboplatin exists in a monomer-dimer equilibrium with an association constant of K (M -1) ≈ 391, a property that accounts for the long-term stability of its ready-to-use infusion solution. When administered in the clinic, carboplatin is believed to exert its biological effects by interacting with genomic DNA and proteins. The slower substitution kinetics of carboplatin, compared to cisplatin, has prompted investigators to focus on mechanisms by which the compound can be activated in vivo. Carbonate, which is in equilibrium with hydrogen carbonate, carbonic acid, and dissolved carbon dioxide, is ubiquitous in biological systems, and is found in high concentrations in the blood, the interstitial fluid, and the cytosol. Activation of carboplatin by carbonate, CO 3 2- (k 1 = 2.04 ± 0.81 × 10 -6 in 24 mM carbonate buffer, pH 7.5 at 37 °C), for example, leads to the formation of platinum species that are more cytotoxic than the parent drug. This short review focuses on the reason for the unusual stability of carboplatin in its aqueous ready-to-use infusion solution, describes the reactions of the drug with biologically common nucleophiles and summarizes the activation chemistry that make the drug more reactive toward substances present in the biological system. |
format |
Text |
author |
Di Pasqua, Anthony J. Goodisman, Jerry Dabrowiak, James C |
author_facet |
Di Pasqua, Anthony J. Goodisman, Jerry Dabrowiak, James C |
author_sort |
Di Pasqua, Anthony J. |
title |
Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell |
title_short |
Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell |
title_full |
Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell |
title_fullStr |
Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell |
title_full_unstemmed |
Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell |
title_sort |
understanding how the platinum anticancer drug carboplatin works: from the bottle to the cell |
publisher |
SURFACE at Syracuse University |
publishDate |
2012 |
url |
https://surface.syr.edu/che/42 https://surface.syr.edu/cgi/viewcontent.cgi?article=1002&context=che |
genre |
Carbonic acid |
genre_facet |
Carbonic acid |
op_source |
Chemistry - Faculty Scholarship |
op_relation |
https://surface.syr.edu/che/42 https://surface.syr.edu/cgi/viewcontent.cgi?article=1002&context=che |
op_rights |
http://creativecommons.org/licenses/by/3.0/ |
op_rightsnorm |
CC-BY |
_version_ |
1766387967950061568 |