About ExerkineAtlas
ExerkineAtlas accompanies the review Exercise as Medicine: The Potential of Exerkines as Therapeutics. For each of the 35 exerkines, it combines curated literature with publication counts from PubMed and registered studies from ClinicalTrials.gov. The publication and trial counts are updated periodically.
The review
Exercise delivers a wide variety of health benefits through many mechanisms, including the release of exerkines, signaling molecules secreted by multiple tissues during physical activity. We evaluated 34 exerkines with therapeutic potential alongside IC7Fc (an engineered IL-6/CNTF derivative), classifying them based on (a) their translational readiness as therapeutics and (b) their primary clinical domains (cardiovascular, metabolic, neurological, musculoskeletal, anti-inflammatory, and oncology). Only four have clear clinical validation, and nine others have reached clinical testing or late preclinical development. Across these molecular entities, three challenges emerge: context-dependent effects, drug-delivery constraints, and network dynamics. We conclude with an assessment of opportunities and strategies for the creation of exerkine-based biomarkers and for using exerkines to facilitate therapeutic discovery. Finally, we present the Exerkine Atlas (https://exerkineatlas.org/), an open-access web resource integrating curated literature and clinical trial data for all 35 molecules.
Methods
Literature compilation
47 review articles on exerkines published within the last five years were compiled through systematic PubMed searches. None focused specifically on therapeutic potential.
Candidate molecules
Molecules described as therapeutically relevant across these reviews were extracted, yielding 45 candidate exerkines. After revision and further investigation, 35 were selected: 34 natural exerkines and IC7Fc, an engineered IL-6/CNTF derivative.
AI-assisted summaries, verified by the authors
NotebookLM (with the review PDFs as sources) produced preliminary summaries of biological roles and therapeutic potential, and OpenEvidence summarized the mechanistic basis for each molecule's classification as an exerkine. Both were chosen for their traceable citations. All outputs were critically reviewed: about 10–15% of NotebookLM outputs contained incorrect assignments, summary inaccuracies or citation errors, while OpenEvidence outputs contained minimal errors. Every reference was individually verified against the primary literature.
Two-axis classification
Each exerkine was assigned a tier of translational readiness (1–4) and a primary therapeutic domain (one of six), based on the strength and stage of the available evidence. Most exerkines act across several organ systems; established secondary evidence is marked in the atlas.
Evidence data
PubMed was searched for each exerkine name in the title or abstract, both alone and in combination with the terms “therapeutic” or “therapy”. At publication, these searches returned 219,280 publications from the last five years across all 35 exerkines, of which 60,594 included therapeutic terminology. The therapeutic share is a keyword-based proxy for translational emphasis, not a measure of clinical evidence.
Registered studies on ClinicalTrials.gov are counted by recruitment status and phase for each exerkine. Counts are keyword-based, so they include every registered study that mentions the molecule, not only trials of it as a therapy.
The figures on this site come from the snapshot of February 2026 and will be refreshed periodically; the date of the current snapshot is always shown next to the numbers.
Team
The authors are supported by National Institutes of Health Common Fund grant U24OD026629 (to D.J-M. and E.A.A.) and the Wu Tsai Human Performance Alliance and the Joe and Clara Tsai Foundation (to E.A.A.). V.M.A. was supported by a Ford Foundation Predoctoral Fellowship and a Knight-Hennessy Scholarship. The authors thank Jimmy Zhen for his assistance with ExerkineAtlas.org.
How to cite
If you use ExerkineAtlas or its data, please cite the review:
Jimenez-Morales D, Arroyo VM, Ashley KI, Altman RB, Ashley EA. Exercise as Medicine: The Potential of Exerkines as Therapeutics. Annu. Rev. Pharmacol. Toxicol. 2027;67. In press. doi:10.1146/annurev-pharmtox-060325-031237
@article{JimenezMorales2027Exerkines,
author = {David Jimenez-Morales and Vidal M. Arroyo and Katryn I. Ashley and Russ B. Altman and Euan A. Ashley},
title = {Exercise as Medicine: The Potential of Exerkines as Therapeutics},
journal = {Annual Review of Pharmacology and Toxicology},
volume = {67},
year = {2027},
doi = {10.1146/annurev-pharmtox-060325-031237},
note = {In press}
}
The article is in press; the DOI will resolve once it is published online.
Download the data
All data shown on this site can be downloaded.