Design, Synthesis, and Biological Evaluation of a Novel Photocaged PI3K Inhibitor toward Precise Cancer Treatment Article Swipe
Kehui Zhang
,
Ming Ji
,
Songwen Lin
,
Shouguo Peng
,
Zhihui Zhang
,
Mingyi Zhang
,
Jingbo Zhang
,
Yan Zhang
,
Deyu Wu
,
Hua Tian
,
Xiaoguang Chen
,
Heng Xu
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1021/acs.jmedchem.0c02186
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1021/acs.jmedchem.0c02186
Aberrant activation of the PI3K pathway has been intensively targeted for cancer therapeutics for decades, leading to more than 40 PI3K inhibitors advanced into clinical trials. However, it is increasingly noticed that PI3K inhibitors often showed limited efficacy as well as a number of serious on-target adverse effects during the clinical development. In this work, we designed and synthesized a novel photocaged PI3K inhibitor 1, which could be readily activated by UV irradiation to release a highly potent PI3K inhibitor 2. Upon UV irradiation, the photocaged inhibitor 1 demonstrated remarkably enhanced antiproliferative activity against multiple cancer cell lines and significant efficacy in the patient-derived tumor organoid model. Furthermore, 1 also showed favorable anticancer activity in an in vivo zebrafish xenograft model. Taken together, the photocaged PI3K inhibitor 1 represents a promising avenue for novel therapeutics toward precise cancer treatment.
Related Topics
Concepts
Chemistry
Zebrafish
PI3K/AKT/mTOR pathway
In vivo
Discovery and development of mTOR inhibitors
Cancer research
Cancer cell
Cancer
Pharmacology
Biochemistry
Signal transduction
Internal medicine
Medicine
Biology
Gene
Biotechnology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/acs.jmedchem.0c02186
- OA Status
- green
- Cited By
- 23
- References
- 30
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3156207684
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3156207684Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1021/acs.jmedchem.0c02186Digital Object Identifier
- Title
-
Design, Synthesis, and Biological Evaluation of a Novel Photocaged PI3K Inhibitor toward Precise Cancer TreatmentWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-04-20Full publication date if available
- Authors
-
Kehui Zhang, Ming Ji, Songwen Lin, Shouguo Peng, Zhihui Zhang, Mingyi Zhang, Jingbo Zhang, Yan Zhang, Deyu Wu, Hua Tian, Xiaoguang Chen, Heng XuList of authors in order
- Landing page
-
https://doi.org/10.1021/acs.jmedchem.0c02186Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.7270/q2833wwpDirect OA link when available
- Concepts
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Chemistry, Zebrafish, PI3K/AKT/mTOR pathway, In vivo, Discovery and development of mTOR inhibitors, Cancer research, Cancer cell, Cancer, Pharmacology, Biochemistry, Signal transduction, Internal medicine, Medicine, Biology, Gene, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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23Total citation count in OpenAlex
- Citations by year (recent)
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2025: 5, 2024: 5, 2023: 7, 2022: 5, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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30Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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