Tumor-targeted dual-action NSAID-platinum(<scp>iv</scp>) anticancer prodrugs

Kastner, Alexander; Mendrina, Theresa; Bachmann, Florian; Berger, Walter; Keppler, Bernhard K.; Heffeter, Petra; Kowol, Christian R.

doi:10.1039/d3qi00968h

Cited by 16 publications

(9 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthetic routes are summarized in Figure S1. This is the first time these three compounds have been reported, and some related Pt–IV compounds have been reported including asplatin, OxAsaOAc, [Pt(NH 3 ) 2 Cl 2 (O 2 C–D-1-MT) 2 ], MalEs/IdoEs, and MalCa/IdoEs . We purified these twin and triplet drugs by HPLC, and the structures were confirmed by 1 H NMR and ESI-MS (Figures S2–S4).…”

Section: Resultsmentioning

confidence: 86%

Platinum Twin and Triplet Drugs Improve Chemoimmunotherapy

Hao,

Li,

Pan

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

Several chemoimmunotherapy regimens have been approved by the U.S. FDA, verifying the great clinical value and potential of the strategy. However, the immunomodulatory function of chemotherapy was insufficient, which did not provide extra overall survival benefits, especially in a head-to-head comparison of chemoimmunotherapy versus immunotherapy. Here, we engineered twin and triplet drugs derived from an immunogenic chemotherapeutic drug (oxaliplatin) and small-molecule inhibitors of negative immunoregulation pathways (COX2 and IDO) in tumors as an improved chemotherapeutic component within chemoimmunotherapy. The twin and triplet drugs exhibited significantly improved synergy with anti-PD-1 in a CT26 colorectal mouse tumor model. Mechanistic analyses revealed that the drug induced immunogenic cell death and restored tumor immune microenvironment toward tumor clearance in vivo, resulting in a great decrease in tumor-infiltrating Tregs and an increase in the CD8+ T/Treg ratio when combined with anti-PD-1. Our work expands the application of platinum twin drugs in combination with an immune checkpoint blockade.

show abstract

Section: Resultsmentioning

confidence: 86%

Platinum Twin and Triplet Drugs Improve Chemoimmunotherapy

Hao,

Li,

Pan

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…1–4 Among these, platinum-based complexes have been widely used in anticancer treatments in clinical settings. 1,5 However, the application and development of platinum-based drugs are limited because of their adverse side effects, such as strong drug resistance and renal toxicity; therefore, alternatives to these drugs are urgently needed. 6 The remarkable anticancer activity and distinct anticancer mechanism of iridium( iii ) (Ir III ) complexes, particularly half-sandwich-shaped Ir III complexes, have made them potential alternatives to cisplatin in recent years.…”

Section: Introductionmentioning

confidence: 99%

The anticancer application of half-sandwich iridium(iii) ferrocene-thiosemicarbazide Schiff base complexes

Liu,

Lv,

Zhang

et al. 2024

Dalton Trans.

View full text Add to dashboard Cite

show abstract

“…To overcome these limitations, several Pt( ii / iv ) coordination compounds have been designed and proposed as antitumor chemotherapeutic agents. 1–5 Extensive studies on unconventional Pt( ii / iv ) coordination compounds, such as riluzole, 6 2-(benzothiazol-2-yl)-phenolato, 7 1,10-phenanthroline derivatives, 8 (8-hydroxy)quinoline derivatives, 9,10 jatrorrhizine/berberine/cryptolepine derivatives, 11 2-(2-pyridyl)benzimidazole, 12 flurbiprofen and zaltoprofen, 13 bis(diisopropylphenyl)iminoacenaphthene, 14 boron dipyrromethene ligands, 15 rhodamine dithiocarbamate, 16 pyridinyl and pyridine ligands, 17 4-phenylbutyric acid, 18 aspirin, 19 coumarin, 20 combretastatin A4, 21 and heptamethine cyanines, 22 have yielded promising results.…”

Section: Introductionmentioning

confidence: 99%