Hypoxia-Activated Prodrug Enabling Synchronous Chemotherapy and HIF-1α Downregulation for Tumor Treatment.

Cell Line, Tumor Down-Regulation / drug effects Doxorubicin / metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Indazoles / metabolism Prodrugs / metabolism Tumor Hypoxia / drug effects

Journal

Bioconjugate chemistry
ISSN: 1520-4812
Titre abrégé: Bioconjug Chem
Pays: United States
ID NLM: 9010319

Informations de publication

Date de publication:
19 05 2021
Historique:
pubmed: 14 4 2021
medline: 14 9 2021
entrez: 13 4 2021
Statut: ppublish

Résumé

The overexpression of HIF-1α in solid tumors due to hypoxia is closely related to drug resistance and consequent treatment failure. Herein, we constructed a hypoxia-activated prodrug named as YC-Dox. This prodrug could be activated under hypoxic conditions and undergo self-immolation to release doxorubicin (Dox) and YC-1 hemisuccinate (YCH-1), which could execute chemotherapy and result in HIF-1α downregulation, respectively. This prodrug is capable of specifically releasing Dox and YCH-1 in response to hypoxia, leading to a substantial synergistic potency and a remarkable cytotoxic selectivity (>8-fold) for hypoxic cancer cells over normoxic healthy cells. The

Identifiants

DOI: 10.1021/acs.bioconjchem.1c00131 PMID: 33847488
pubmed: 33847488
doi: 10.1021/acs.bioconjchem.1c00131
doi:

Substances chimiques

HIF1A protein, human 0
Hypoxia-Inducible Factor 1, alpha Subunit 0
Indazoles 0
Prodrugs 0
3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole 154453-18-6
Doxorubicin 80168379AG

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

983-990

Auteurs

Xiangjie Luo (X)

The Key Laboratory for Chemical Biology of Fujian Province, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Ao Li (A)

The Key Laboratory for Chemical Biology of Fujian Province, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Xiaoqin Chi (X)

Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.

Yaying Lin (Y)

The Key Laboratory for Chemical Biology of Fujian Province, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Xing Liu (X)

The Key Laboratory for Chemical Biology of Fujian Province, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Lifan Zhang (L)

Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.

Xinhui Su (X)

Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.
ORCID: 0000-0003-4355-6052

Zhenyu Yin (Z)

Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.

Hongyu Lin (H)

The Key Laboratory for Chemical Biology of Fujian Province, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Jinhao Gao (J)

The Key Laboratory for Chemical Biology of Fujian Province, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
ORCID: 0000-0003-3215-7013

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Glucides › Hétérosides › Aminosides › Anthracyclines › Daunorubicine › Doxorubicine › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Facteur-1 induit par l'hypoxie › Sous-unité alpha du facteur-1 induit par l'hypoxie › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indazoles › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Préparations pharmaceutiques › Promédicaments › Hypoxia-Activated Prodrug Enabling Synchronous...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Respiration cellulaire › Hypoxie cellulaire › Hypoxie tumorale › Hypoxia-Activated Prodrug Enabling Synchronous...