PUBLICATION
CAIXplatins: Highly Potent Platinum(IV) Prodrugs Selective Against Carbonic Anhydrase IX for the Treatment of Hypoxic Tumors
- Authors
- Cao, Q., Zhou, D.J., Pan, Z.Y., Yang, G.G., Zhang, H., Ji, L.N., Mao, Z.W.
- ID
- ZDB-PUB-210319-26
- Date
- 2020
- Source
- Angewandte Chemie (International ed. in English) 59: 18556-18562 (Journal)
- Registered Authors
- Keywords
- cancer, carbonic anhydrase IX, hypoxia, platinum, prodrugs
- MeSH Terms
-
- Animals
- Carbonic Anhydrase IX/antagonists & inhibitors*
- Carbonic Anhydrase IX/metabolism
- Cell Hypoxia*
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cisplatin/pharmacology
- Cluster Analysis
- Coordination Complexes/chemistry*
- Coordination Complexes/metabolism
- Coordination Complexes/pharmacology
- Coordination Complexes/therapeutic use
- Drug Screening Assays, Antitumor
- Humans
- Larva/drug effects
- Larva/metabolism
- Mice
- Mice, Nude
- Neoplasms/drug therapy
- Neoplasms/pathology
- Platinum/chemistry*
- Prodrugs/chemistry*
- Prodrugs/metabolism
- Prodrugs/pharmacology
- Prodrugs/therapeutic use
- Proteome/analysis
- Proteome/drug effects
- Proteomics
- Zebrafish/growth & development
- PubMed
- 32557982 Full text @ Angew. Chem. Int. Ed. Engl.
Citation
Cao, Q., Zhou, D.J., Pan, Z.Y., Yang, G.G., Zhang, H., Ji, L.N., Mao, Z.W. (2020) CAIXplatins: Highly Potent Platinum(IV) Prodrugs Selective Against Carbonic Anhydrase IX for the Treatment of Hypoxic Tumors. Angewandte Chemie (International ed. in English). 59:18556-18562.
Abstract
Hypoxia and the acidic microenvironment play a vital role in tumor metastasis and angiogenesis, generally compromising the chemotherapeutic efficacy. This provides a tantalizing angle for the design of platinum(IV) prodrugs for the effective and selective killing of solid tumors. Herein, two carbonic anhydrase IX (CAIX)-targeting platinum(IV) prodrugs have been developed, named as CAIXplatins. Based on their strong affinity for and inhibition of CAIX, CAIXplatins can not only overcome hypoxia and the acidic microenvironment, but also inhibit metabolic pathways of hypoxic cancer cells, resulting in a significantly enhanced therapeutic effect on hypoxic MDA-MB-231 tumors both in vitro and in vivo compared with cisplatin/oxaliplatin, accompanied with excellent anti-metastasis and anti-angiogenesis activities. Furthermore, the cancer selectivity indexes of CAIXplatins are 70-90 times higher than those of cisplatin/oxaliplatin with effectively alleviated side-effects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping