Evidence map›Paper›PMID 40214085›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Reactive Cysteines in Proteins are the Dominant Reductants for Platinum(IV) Prodrug Activation in Live Cells.

Shu Chen, Wang Peng, Houzong Yao, Zhiqin Deng, Zhao Yue, Gongyuan Liu, Jiaqian Xu, Naixin Lin, Weikang Xu, Jianbo Yue and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Shu ChenDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Wang PengCity University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China.
Houzong YaoDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Zhiqin DengDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Zhao YueDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Gongyuan LiuDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Jiaqian XuDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Naixin LinCity University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China.
Weikang XuDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.
Jianbo YueCity University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China.
Guangyu ZhuDepartment of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P.R. China.

Funding

City University of Hong Kong 7020014Hong Kong Research Grants Council 11302221Hong Kong Research Grants Council 11304923Hong Kong Research Grants Council 11306724Hong Kong Research Grants Council 11313222Hong Kong Research Grants Council C1018-23GNational Natural Science Foundation of China 22077108National Natural Science Foundation of China 22277103Science Technology and Innovation Committee of Shenzhen Municipality JCYJ20210324120004011
6 · The paper itself

Abstract

The intracellular reduction of Pt(IV) prodrugs is crucial for their anticancer efficacy. However, the major components responsible for the reduction of Pt(IV) complexes within live cells remain elusive. Herein, we developed an aminoluciferin-functionalized Pt(IV) complex, Pt-Luc, that can be used as a bioluminescent reporter for real-time monitoring of Pt(IV) reduction in live cancer cells by capturing immediate bioluminescent signals from the released aminoluciferin. Utilizing this powerful reporter, we found that the reduction of Pt(IV) prodrugs in live cancer cells significantly slows down when cysteine levels are reduced, while the levels of glutathione do not impact the reduction rate. Further investigation reveals that reactive cysteines in proteins, rather than small-molecule thiols, play a primary role in reducing the Pt(IV) complex. In vivo studies reveal a substantial 63% decrease in bioluminescence from Pt-Luc in thiol-blocking tumors in mice, reinforcing the pivotal role of reactive cysteines in Pt(IV) reduction. This study provides valuable insights into the activation mechanisms of Pt(IV) prodrugs in live cells and in vivo, enhancing our understanding of prodrug activation beyond buffer systems or fixed cells.

Indexed as

Antineoplastic AgentsCysteineOrganoplatinum CompoundsProdrugsProteinsReducing AgentsAnimalsCell Line, TumorHumansMiceOxidation-ReductionAntineoplastic AgentsCysteineOrganoplatinum CompoundsProdrugsProteinsReducing AgentsBioluminescence imagingLive cellsPlatinum(IV) prodrugPlatinum(IV) reductionProdrug activation

Identifiers

PMID40214085
PMCPMC12171337

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.