Structural insight into SSE15206 in complex with tubulin provides a rational design for pyrazolinethioamides as tubulin polymerization inhibitors
Background: Tubulin protein is a promising target for antitumor drugs. Some tubulin inhibitors targeting the colchicine binding site are not substrates of the multidrug-resistance efflux pump, which can overcome the mechanism of drug resistance mediated by P-glycoprotein. Methodology/results: SSE15206 is a colchicine binding site inhibitor with antiproliferative activity against different drug-resistant cell lines. Unfortunately, the lack of detailed interaction information about SSE15206 in complex with tubulin impeded the development of potent drugs that possess similar scaffolds. Herein, the authors report the crystal structure of the tubulin-SSE15206 complex at a resolution of 2.8 Å. Conclusion: The complex structure reveals the intermolecular interactions between SSE15206 and tubulin, providing a rationale for the development of pyrazolinethioamides as tubulin polymerization inhibitors and to overcome multidrug resistance.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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Enthalten in: |
Future medicinal chemistry - 14(2022), 11 vom: 18. Juni, Seite 785-794 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Ma, Lingling [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 19.05.2022 Date Revised 06.09.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.4155/fmc-2021-0124 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM340351241 |
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520 | |a Background: Tubulin protein is a promising target for antitumor drugs. Some tubulin inhibitors targeting the colchicine binding site are not substrates of the multidrug-resistance efflux pump, which can overcome the mechanism of drug resistance mediated by P-glycoprotein. Methodology/results: SSE15206 is a colchicine binding site inhibitor with antiproliferative activity against different drug-resistant cell lines. Unfortunately, the lack of detailed interaction information about SSE15206 in complex with tubulin impeded the development of potent drugs that possess similar scaffolds. Herein, the authors report the crystal structure of the tubulin-SSE15206 complex at a resolution of 2.8 Å. Conclusion: The complex structure reveals the intermolecular interactions between SSE15206 and tubulin, providing a rationale for the development of pyrazolinethioamides as tubulin polymerization inhibitors and to overcome multidrug resistance | ||
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700 | 1 | |a Huang, Ridong |e verfasserin |4 aut | |
700 | 1 | |a Su, Tao |e verfasserin |4 aut | |
700 | 1 | |a Feng, Jianrong |e verfasserin |4 aut | |
700 | 1 | |a Sun, Qiu |e verfasserin |4 aut | |
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