Evidence map›Paper›PMID 41330895›Full record

ArticleNature communications2025

Understanding interspecies drug response variations between human and rodent P2X7 receptors.

Chang-Run Guo, Danqi Sheng, Ji-Yuan Li, Tian-Tian Li, Jia-Bao Yao, Rui Zhang, Ye Huang, Ying-Ying Zhao, Dong-Ping Wang, Jie Chen and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. 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

19 authors.

Chang-Run Guo *School of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.ORCID http://orcid.org/0009-0004-2348-3591
Danqi Sheng *State Key Laboratory of Genetics and Development of Complex Phenotypes, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Ji-Yuan Li *School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Tian-Tian Li *School of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Jia-Bao YaoSchool of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Rui ZhangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Ye HuangSchool of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Ying-Ying ZhaoSchool of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Dong-Ping WangSchool of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Jie ChenSchool of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Jian LiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Jiang WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0003-1705-4905
Yu ZhouSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.ORCID http://orcid.org/0000-0002-7684-2939
Cheng ShenState Key Laboratory of Genetics and Development of Complex Phenotypes, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Fei JinState Key Laboratory of Genetics and Development of Complex Phenotypes, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Peng CaoHospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.ORCID http://orcid.org/0000-0002-2044-3074
Motoyuki HattoriState Key Laboratory of Genetics and Development of Complex Phenotypes, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai, China. hattorim@fudan.edu.cn.ORCID http://orcid.org/0000-0002-5327-5337
Hong LiuSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China. hliu@simm.ac.cn.ORCID http://orcid.org/0000-0003-3685-6268
Ye YuSchool of Basic Medicine and Clinical Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. yuye@cpu.edu.cn.ORCID http://orcid.org/0000-0002-4054-8543

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32371289
6 · The paper itself

Abstract

Despite intensive development, P2X7 modulators have struggled in translation due to human genetic variability and species-dependent drug responses. Here, we identify PSFL1191, a portal-of-central-pocket (PCP)-site inhibitor selective for human and panda P2X7, but inactive against rodents. Cryo-EM structures revealed two distinct PCP sub-pockets: PCP1, a rigid base pocket demanding precise steric complementarity with PSFL1191, and PCP2, a conserved middle cavity targeted by JNJ-54175446, a clinical candidate unaffected by species differences. Species selectivity maps to a deep PCP1 motif (V312-Y295-M105-F103-P96). In P2rx7

Indexed as

BerberinePurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7Allosteric SiteAnimalsCryoelectron MicroscopyDrug Evaluation, PreclinicalHumansMiceMice, TransgenicSpecies SpecificityUrsidaeWound HealingBerberineP2RX7 protein, humanPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7

Identifiers

PMID41330895
PMCPMC12673082

What OpenQuestion holds

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Registered trials

None linked

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.