Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (733 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Pro-Drug; Pro Drug; Drug Precursor; Precursor, Drug; Prodrug; Drug Precursors; Precursors, Drug; Pro-Drugs.
Where it fits in the MeSH classification
- Broader topics
- Pharmaceutical Preparations
- Narrower topics
- ProTides
Research landscape
PubMed indexes 15,397 records tagged with the MeSH heading “Prodrugs” (counts retrieved 2026-10-31). 3,934 of them (25.6%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 4,757 records.
Reviews account for 2,128 records (13.8%) and meta-analyses for 14. Randomized controlled trials number 527 (3.4%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 2,644 |
| 2000-2009 | 4,062 |
| 2010-2019 | 4,757 |
| 2020 onward | 3,934 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,128 | 13.8% |
| Meta-analyses | 14 | 0.1% |
| Randomized controlled trials | 527 | 3.4% |
Method: PubMed query "Prodrugs"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy | 2023 | Research article Design not recorded in structured metadata | 124 | cc by PMID 37626073 · DOI · PMC10457322 |
| Cyclic Ruthenium-Peptide Conjugates as Integrin-Targeting Phototherapeutic Prodrugs for the Treatment of Brain Tumors | 2023 | Research article Design not recorded in structured metadata | 65 | cc by PMID 37379365 · DOI · PMC10347550 |
| Prodrug Integrated Envelope on Probiotics to Enhance Target Therapy for Ulcerative Colitis | 2023 | Research article Design not recorded in structured metadata | 62 | cc by PMID 36507607 · DOI · PMC9896077 |
| DCAF11-dependent molecular glue degrader activated by glutathionylation | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42557329 · DOI · PMC13600927 |
A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Precise and efficient image-guided immunotherapy holds great promise for cancer treatment.
- Closing excerpt
- Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (193 words)
Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) and a hypoxia-responsive prodrug for multifunctional image-guided combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence and photoacoustic (PA) brightness for the strong light absorption ability, as well as amplified type I and type II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating the high-performance AIEgen with a hypoxia-responsive paclitaxel (PTX) prodrug into nanoparticles, and further camouflaging with macrophage cell membrane, a tumor-targeting theranostic agent is built. The integration of fluorescence and PA imaging helps to delineate tumor site sensitively, providing accurate guidance for tumor treatment. The light-induced PDT effect could consume the local oxygen and lead to severer hypoxia, accelerating the release of PTX drug. As a result, the combination of PDT and PTX chemotherapy induces immunogenic cancer cell death, which could not only elicit strong antitumor immunity to suppress the primary tumor, but also inhibit the growth of distant tumor in 4T1 tumor-bearing female mice. Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37626073 · DOI · PMC10457322
Cyclic Ruthenium-Peptide Conjugates as Integrin-Targeting Phototherapeutic Prodrugs for the Treatment of Brain Tumors [2]
Abstract reading summary — source excerpts
- Opening excerpt
- To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal.
- Closing excerpt
- Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (251 words)
To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 μM for the binding of Λ-[1]Cl2 to αIIbβ3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37379365 · DOI · PMC10347550
Prodrug Integrated Envelope on Probiotics to Enhance Target Therapy for Ulcerative Colitis [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Ulcerative colitis (UC), affecting millions of patients worldwide, is associated with disorders of the gut microbiota.
- Closing excerpt
- These results provide ample shreds of evidence of the therapeutic effect on UC, therefore, demonstrate a great promise as the potential therapeutic strategy for UC treatment.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (153 words)
Ulcerative colitis (UC), affecting millions of patients worldwide, is associated with disorders of the gut microbiota. Probiotics-based therapy positively regulating the community structure of gut microbiota is regarded as an efficient intervention for UC. However, oral probiotics delivery is restricted by limited bioactivity, short retention time, complex pathological condition, and single therapeutic efficacy. Here, a bioengineered probiotic decorated with a multifunctional prodrug coating is constructed to ameliorate the aforementioned shortcomings. The results of UC mice induced by dextran sulfate sodium demonstrate that the intrinsic features of the fabricated coating integrate gut microbes protection, colon-targeted drug release, prolonged drug retention, and inflammation regulation. In parallel, the probiotics Lactobacillus rhamnosus GG (LGG) could regulate the composition of the gut microbiota and improve epithelial barrier function, thereby synergistically ameliorating UC. These results provide ample shreds of evidence of the therapeutic effect on UC, therefore, demonstrate a great promise as the potential therapeutic strategy for UC treatment.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36507607 · DOI · PMC9896077
DCAF11-dependent molecular glue degrader activated by glutathionylation [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Targeted protein degradation is a powerful pharmacological strategy that harnesses the ubiquitin proteasome system to eliminate disease-relevant proteins, including otherwise undruggable proteins1.
- Closing excerpt
- Collectively, these findings establish that metabolically activated compounds can redirect E3 ligase function, thereby expanding the scope of targeted protein degradation and chemically induced proximity.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (136 words)
Targeted protein degradation is a powerful pharmacological strategy that harnesses the ubiquitin proteasome system to eliminate disease-relevant proteins, including otherwise undruggable proteins1. Here we report an unbiased and broadly applicable platform for the systematic discovery of molecular glues across diverse E3 ligases. Using multiplexed mass spectrometry-based chemical screening, we identified M12, a molecular glue that reprogrammes the E3 ligase DCAF11 to degrade DDX18. Mechanistically, M12 functions as a prodrug that is activated through glutathione S-transferase-mediated glutathionylation. The glutathione moiety binds to an evolutionary conserved glutathione-binding site on DCAF11, and the exposed M12 moiety facilitates neo-substrate recruitment. We demonstrate that this glutathione-dependent mechanism readily enables targeted degradation of a range of proteins. Collectively, these findings establish that metabolically activated compounds can redirect E3 ligase function, thereby expanding the scope of targeted protein degradation and chemically induced proximity.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42557329 · DOI · PMC13600927
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future [5]
- Research article The expanding role of prodrugs in contemporary drug design and development [6]
- Research article From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity [7]
- Research article Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in the Last Decade [8]
- Research article Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update [9]
- Research article Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus [10]
References
- Kang X, Zhang Y, Song J, Wang L, Li W, Qi J, et al.. A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy. . 2023. PMID 37626073 · DOI · PMC10457322
- Zhang L, Wang P, Zhou XQ, Bretin L, Zeng X, Husiev Y, et al.. Cyclic Ruthenium-Peptide Conjugates as Integrin-Targeting Phototherapeutic Prodrugs for the Treatment of Brain Tumors. . 2023. PMID 37379365 · DOI · PMC10347550
- Zhang K, Zhu L, Zhong Y, Xu L, Lang C, Chen J, et al.. Prodrug Integrated Envelope on Probiotics to Enhance Target Therapy for Ulcerative Colitis. . 2023. PMID 36507607 · DOI · PMC9896077
- Yoon H, Wachter F, Barrett KA, Jin C, Rodríguez-Pöhnlein A, Rutter JC, et al.. DCAF11-dependent molecular glue degrader activated by glutathionylation. . 2026. PMID 42557329 · DOI · PMC13600927
- Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P, Vymetalkova V. 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future. Pharmacol Ther. 2020. PMID 31756363 · DOI
- Rautio J, Meanwell NA, Di L, Hageman MJ. The expanding role of prodrugs in contemporary drug design and development. Nat Rev Drug Discov. 2018. PMID 29700501 · DOI
- Trevaskis NL, Kaminskas LM, Porter CJ. From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity. Nat Rev Drug Discov. 2015. PMID 26471369 · DOI
- Savelieff MG, Nam G, Kang J, Lee HJ, Lee M, Lim MH. Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in the Last Decade. Chem Rev. 2019. PMID 30095897 · DOI
- Lee CR, Luzum JA, Sangkuhl K, Gammal RS, Sabatine MS, Stein CM, et al.. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022. PMID 35034351 · DOI · PMC9287492
- Ray AS, Fordyce MW, Hitchcock MJ. Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus. Antiviral Res. 2016. PMID 26640223 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.