Evidence map›Paper›PMID 40493099›Full record

ArticleNatural products and bioprospecting2025

Design of 20-deoxyingenol-esters-based PKC agonists and their lysosome biogenesis-enhancing activity.

Jia-Jia Wan, Qiu-Yuan Yin, Mao Sun, Cui-Shan Zhang, Hao-Jing Zang, Pei-Tong Yao, Ming-Rui Yuan, Ding-Kang Chen, Feng Guo, Qun Chen and 6 more

Erratum issuedAbstract read
In one paragraph

Article in Natural products and bioprospecting, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Ingenane Diterpenoids fromMolecules (Basel, Switzerland) · 2026
    Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Jia-Jia Wan *State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Qiu-Yuan Yin *School of Life Sciences, Yunnan University, Kunming, 650091, China.
Mao Sun *An Shun City People's Hospital, Anshun, 561000, China.
Cui-Shan Zhang *State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Hao-Jing ZangState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Pei-Tong YaoState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Ming-Rui YuanState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Ding-Kang ChenState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Feng GuoState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Qun ChenState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Bo-Wen OuyangState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Zi-Fei XuState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Ming-Ming CaoState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
Chong-Lin YangSchool of Life Sciences, Yunnan University, Kunming, 650091, China. clyang@ynu.edu.cn.
Xiao-Jiang HaoState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. haoxj@mail.kib.ac.cn.
Ying-Tong DiState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. diyt@mail.kib.ac.cn.ORCID http://orcid.org/0000-0001-5766-0198

Funding

CAMS Innovation Fund for Medical Sciences 2021-I2M-5-004Guizhou Provincial Science and Technology Department QKHJC-ZK[2021]YB557Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research YKKF2024005National Natural Science Foundation of China 22177050National Natural Science Foundation of China 82293683Project of Yunnan Characteristic Plant Screening and R&D Service 2022YKZY001Youth and Middle-aged Scientific and Technological Innovation Leading Talents Program of the Corps 202105AC160044Yunnan Provincial Science and Technology Department 202201AS070040Yunnan Provincial Science and Technology Department 202203AC100009Yunnan Provincial Science and Technology Department 202302AA310035
6 · The paper itself

Abstract

The activation of conventional (α) and novel (δ) protein kinase C (PKC) isoforms promotes lysosomal biogenesis, a critical process for clearance of pathogenic protein aggregates including β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in neurodegenerative disorders. Notably, PKC activators HEP14/15, characterized by 20-methyl moiety, fail to establish classical C1B domain pharmacophore interactions, suggesting a non-canonical activation mechanism. In this study, structural diversification of 20-deoxyingenol through esterification and acetonide protection yielded 18 new derivatives (2-19). Systematic screening revealed their lysosome-promoting activities, with structure-activity relationship analysis identifying compounds 4 and 18 as superior autophagy inducers. At 20 μM, these derivatives enhanced autophagic flux by 2.45-fold and 2.31-fold versus vehicle control. Moreover, compounds 4 and 18 exhibited a dose-dependent increase in lysosome numbers, promoted TFEB nuclear translocation, and enhanced lysosome-mediated lipid droplet clearance. Western blot analysis further revealed that compounds 4/18 upregulated proteins associated with the autophagy-lysosome system, suggesting their potential as promising autophagy inducers. Mechanistically, molecular docking simulations indicated thier high-affinity binding to PKCδ, which may explain their autophagy-enhancing properties.

Indexed as

20-deoxyingenolAmino acidPKCδSAR

Identifiers

PMID40493099
PMCPMC12151967

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.