Thiostrepton
A sulfur-rich bacterial antibiotic used on animals, its many laboratory targets, and the first human trial of a formulated version
Thiostrepton is a large, sulfur-rich peptide antibiotic made by Streptomyces bacteria. It stops bacteria making proteins by jamming their ribosome, and in the US it is approved only as one ingredient of prescription ointments for dogs, cats and cattle. Laboratories use it to block FOXM1, a transcription factor that drives many cancers, and it reduces inflammation in mouse models. Poor solubility has kept it out of human medicine; a formulated version given into the chest cavity reached a first small trial in mesothelioma in 2026.
Used in human trials: 90 mg, Once weekly, Intrapleural (formulated product RSO-021) (Study: relapsed pleural mesothelioma with pleural effusion, phase 1...) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Thiostrepton is one of the thiopeptides, antibiotics that bacteria build on the ribosome and then heavily rework into rings studded with sulfur-containing thiazole groups. It is made by Streptomyces bacteria. In bacteria it binds the large ribosomal subunit where elongation factors dock, so protein synthesis stalls. It mainly hits Gram-positive bacteria, though laboratory work shows it can reach some Gram-negative species, including multidrug-resistant Pseudomonas, by slipping in through their iron-uptake receptors.
Its only licensed use is veterinary. US federal regulations list it as one of four ingredients, with nystatin, neomycin and triamcinolone, in prescription ointments for dogs and cats (skin, ears, anal glands and interdigital cysts) and in an eye ointment for dogs, cats and cattle. It has never been approved as a human medicine, largely because it barely dissolves in water and is poorly absorbed.
Most current research is about cancer. Thiostrepton suppresses FOXM1, a transcription factor that pushes cancer cells through division, and it binds the protein directly. It also inhibits the proteasome and forms covalent bonds with peroxiredoxin 3, a mitochondrial antioxidant enzyme, which leaves cancer cells exposed to their own oxidative stress. Nearly all of this work is in cell lines and mice, often with the drug packed into micelles or nanoparticles so it can be injected.
A second line of work concerns inflammation. In mice thiostrepton reduced psoriasis-like skin inflammation by blocking Toll-like receptors 7 to 9, eased colitis by breaking down the Th17 regulator RORgammat, and extended survival in sepsis. A 2025 review collects these models and repeats that bioavailability is the obstacle.
The first human data come from a phase 1 trial in relapsed pleural mesothelioma, published in 2026, in which a formulated thiostrepton product called RSO-021 was given weekly into the pleural space. It was well tolerated and two thirds of patients had stable or shrinking disease at 12 weeks. That is a single small dose-finding study, listed under References because its title does not name thiostrepton, and it does not make thiostrepton a treatment for anything.
Mechanism of Action
Thiostrepton has one well-defined target in bacteria and several in human cells, which is why it appears in antibiotic, cancer and inflammation research.
Bacterial ribosome
It binds 23S ribosomal RNA and protein L11 where elongation factors dock, stalling protein synthesis; the parasite apicoplast's ribosome is hit the same way.
FOXM1
In cancer cells it lowers FOXM1 expression and binds the FOXM1 protein, blocking its access to target genes.
Oxidative stress
It bonds covalently to peroxiredoxin 3 in mitochondria and inhibits the proteasome, leaving cells exposed to their own reactive oxygen species.
Innate immune signalling
It blocks Toll-like receptors 7 to 9 and promotes breakdown of RORgammat, damping inflammatory signalling in mouse models.
Published Research
These are studies of thiostrepton read from their PubMed abstracts: how it acts on bacterial ribosomes and its activity against Pseudomonas, gonorrhoea, mycobacteria and malaria parasites; the cancer cell work on FOXM1 and peroxiredoxin 3; mouse and rat models of tumours, psoriasis, colitis, sepsis and endometriosis; a skin-cell toxicity study; and two reviews. Each card names the species or cells used. The 2026 phase 1 trial is under References.
Mode of action, uses and the formulation problem
This review describes thiostrepton as a veterinary antibiotic that stops bacterial protein synthesis by keeping GTP-dependent elongation factors off the ribosome, mainly in Gram-positive bacteria. It also blocks protein synthesis in the malaria parasite's apicoplast, inhibits the cancer-linked transcription factor FOXM1, and binds peroxiredoxin 3 and the proteasome. It names poor solubility as the main barrier to drug development and points to semi-synthetic analogues and micelle carriers as ways round it.
Anti-inflammatory activity across disease models
A review of thiostrepton's anti-inflammatory effects in animal and cell models of fatty liver disease, inflammatory bowel disease, sepsis, psoriasis-like skin inflammation and periodontitis. It describes the compound as a safe antimicrobial in veterinary practice whose human use has been held back by poor solubility and bioavailability.
How it jams the ribosome
Working with archaeal mutants highly resistant to thiostrepton and with the bacterial protein, this study found that resistance came from a single change at a conserved proline in ribosomal protein L11. Thiostrepton binds mainly to 23S ribosomal RNA, but it appears to stop protein synthesis by blocking a shape change in L11 at the ribosome's GTPase centre; eukaryotic L11 lacks that proline, which may explain why human ribosomes are spared.
Gets into Pseudomonas through its iron receptors
Long thought inactive against Gram-negative bacteria, thiostrepton inhibited all 96 multidrug-resistant Pseudomonas aeruginosa clinical isolates tested at low micromolar concentrations, and some Acinetobacter baumannii isolates. It crossed the outer membrane through the pyoverdine (siderophore) receptors FpvA and FpvB, so it worked best when iron was scarce, and the iron chelators deferiprone and deferasirox boosted its activity.
Blocks the stress response in gonorrhoea
A clinical isolate of Neisseria gonorrhoeae was highly sensitive to thiostrepton in the laboratory. The drug prevented the bacterium's stringent response, a starvation programme linked to antibiotic tolerance, and unlike other antibiotics tested it did not induce tolerance or persistence. It also turned down genes the bacterium uses to interact with its host.
Kills the malaria parasite through its plastid
Thiostrepton inhibited growth of Plasmodium falciparum in red-cell culture at micromolar concentrations, about ten times lower than those that affected the parasite's overall protein synthesis. RNA made by the parasite's plastid-like organelle disappeared within six hours while nuclear transcripts held steady, consistent with a selective hit on the plastid's ribosomes.
Turns down FOXM1 in breast cancer cells
In human breast cancer cell lines, thiostrepton lowered FOXM1 expression in a time- and dose-dependent way, mostly at the level of the gene's transcription, and caused cell-cycle arrest and death through caspase-dependent and caspase-independent routes. It reduced migration and transformation, its effect was overridden by a constitutively active FOXM1, and it left non-cancerous MCF-10A breast cells largely unaffected.
Binds the FOXM1 protein directly
Biophysical experiments showed thiostrepton interacting directly with FOXM1 protein from MCF-7 breast cancer cells and preventing it from binding its target sites in the genome. The authors present this as evidence that a transcription factor, usually hard to drug, can be blocked by a small natural product.
Peroxiredoxin 3 as a second target in mesothelioma
In human malignant mesothelioma cells, thiostrepton's suppression of FOXM1 depended on oxidative stress and was undone by the antioxidant N-acetylcysteine. The drug formed covalent bonds with cysteines in the mitochondrial antioxidant enzyme peroxiredoxin 3, and lowering the partner enzyme thioredoxin 2 with gentian violet made thiostrepton markedly more toxic to the cells.
Damages mitochondria in liver cancer cells
Picked out by a computational drug-repurposing screen, thiostrepton slowed proliferation, arrested the cycle, triggered apoptosis and reduced migration of hepatocellular carcinoma cell lines. It damaged mitochondria and raised reactive oxygen species; the antioxidant N-acetylcysteine reversed the damage, and blocking autophagy strengthened the anticancer effect.
Toxic to human skin cells under oxidative stress
In immortalised human keratinocytes (HaCaT) exposed to hydrogen peroxide, thiostrepton lowered the antioxidants superoxide dismutase, glutathione and catalase, raised the lipid-damage marker malondialdehyde, disturbed mitochondrial structure and membrane potential, and shifted ferroptosis-related genes, driving the cells toward death. The finding bears on any skin use.
Active against Mycobacterium abscessus in zebrafish
Thiostrepton inhibited Mycobacterium abscessus, a hard-to-treat multidrug-resistant species, including subspecies, clinical isolates and resistant mutants, in culture and inside macrophages, where it also lowered inflammatory cytokines. It reduced infection in a zebrafish model. The abstract describes thiostrepton as FDA-approved, which applies to its veterinary use only.
Packaged in micelles, it slowed tumours in mice
To get round its insolubility, thiostrepton was loaded into lipid-PEG micelles about 100 nm across. In mice carrying human MDA-MB-231 breast and HepG2 liver cancer xenografts, the particles collected in tumours within four hours, stayed for at least a day, slowed tumour growth with repeated dosing, lowered FOXM1 in the tumours and increased cell death.
Calms psoriasis-like inflammation in mice
Found by a gene-expression search for drugs that act like bortezomib, thiostrepton blocked activation of Toll-like receptors 7, 8 and 9 in cell assays and dendritic cells, partly by inhibiting the proteasome and partly by stopping endosomes from acidifying. It was less toxic to dendritic cells than bortezomib and reduced psoriasis-like skin inflammation induced by LL37 or imiquimod in mouse models.
Eases colitis in two mouse models
Thiostrepton reduced inflammation in mice with dextran sulfate colitis and in a T-cell transfer colitis model. It caused the transcription factor RORgammat to be tagged for destruction, cutting IL-17 production by Th17 cells, gamma-delta T cells and type 3 innate lymphoid cells, and it partly corrected the gut-bacteria imbalance, which contributed to the benefit in microbiota-transfer experiments.
Micelle form extends survival in septic mice
In mice with polymicrobial sepsis from caecal ligation and puncture, thiostrepton in phospholipid micelles extended median survival from 31 to 44 hours, lowered the number of bacteria in the blood and peritoneal fluid and reduced inflammatory markers. The authors chose it because it is both an antibiotic and a Toll-like receptor 9 inhibitor.
Shrinks endometriosis lesions in rats
Despite its title, this was a rat study. In 50 Wistar rats with surgically induced endometriosis, FOXM1 was concentrated in the nuclei of the ectopic tissue and appeared to act through an ERK/FOXM1/MMP9 pathway; injections of thiostrepton into the abdomen lowered FOXM1, MMP9 and Bcl-2 in the lesions in a concentration-dependent way.
Dosing Data
Thiostrepton is not approved for human use. The one amount below comes from the only published human trial, a phase 1 study of a formulated product given into the chest cavity of patients with mesothelioma. Its US veterinary ointments are not for human use.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: no product of Thiostrepton is approved for people, and we hold no copy of a veterinary label or a published test that says what forms it is sold in (its approvals are under Legal status below). A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intrapleural (formulated product rso-021)). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Thiostrepton, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Thiostrepton stays intact once mixed.
How it is taken
As it was given in human studies: Intrapleural (formulated product RSO-021) (Once weekly; Study: relapsed pleural mesothelioma with pleural effusion, phase 1 (NCT05278975)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: relapsed pleural mesothelioma with pleural effusion, phase 1 (NCT05278975): Disease control assessed at 12 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Thiostrepton. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Weekly intrapleural RSO-021 was reported as well tolerated in the phase 1 mesothelioma trial (NCT05278975, listed under References); In human keratinocytes under oxidative stress it depleted antioxidants and damaged mitochondria (PMID 38969192). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Thiostrepton. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Human safety data are limited to one small phase 1 trial; the rest comes from cells and animals”).
Interactions
Unknown: a PubMed search for human interaction studies of Thiostrepton (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Thiostrepton products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Thiostrepton's expected mass, 1,664.9 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved for human use: Drugs@FDA (openFDA) and EMA's Article 57 product data hold no human-medicine record (October 29, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Human safety data are limited to one small phase 1 trial; the rest comes from cells and animals.
Contraindications & Cautions
There is no human product or label.
Legal Status
Thiostrepton is a veterinary antibiotic ingredient. It has no human approval anywhere in the sources read.
Frequently Asked Questions
?What is thiostrepton?
A sulfur-rich thiopeptide antibiotic made by Streptomyces bacteria. It stops bacteria making proteins by binding their ribosome.
?Is thiostrepton approved for humans?
No. In the US it is approved only as one ingredient of prescription veterinary ointments for dogs, cats and, for the eye ointment, cattle.
?Why is it studied in cancer?
It suppresses and binds FOXM1, a transcription factor that drives cancer cell division, and it attacks the antioxidant enzyme peroxiredoxin 3. Most of this work is in cell lines and mice.
?Has it been tested in people?
Once, as far as we found: a 2026 phase 1 trial in mesothelioma gave a formulated version, RSO-021, into the pleural space weekly. It was well tolerated in that small group.
?Why has it not become a human drug?
It barely dissolves in water and is poorly absorbed, so it is hard to deliver. Researchers have used micelles, nanoparticles and semi-synthetic analogues to get round this.
?Does it work against Gram-negative bacteria?
Mostly no, but in the laboratory it entered Pseudomonas and Acinetobacter through their iron-uptake receptors and inhibited multidrug-resistant isolates when iron was scarce.
References
- [other] PubChem CID 16129666, Thiostrepton: formula C72H85N19O18S5, molecular weight 1664.9. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/16129666
- [review] Bailly C. "The bacterial thiopeptide thiostrepton. An update of its mode of action, pharmacological properties and applications." Eur J Pharmacol, 2022;914:174661. PMID: 34863996.
- [review] Asikaer A, et al. "Thiostrepton: multifaceted biological activities and its applications in treatment of inflammatory diseases." Inflammopharmacology, 2025;33(1):183-194. PMID: 39487942.
- [pubmed] Porse BT, et al. "The antibiotic thiostrepton inhibits a functional transition within protein L11 at the ribosomal GTPase centre." J Mol Biol, 1998;276(2):391-404. PMID: 9512711.
- [pubmed] Ranieri MRM, et al. "Thiostrepton Hijacks Pyoverdine Receptors To Inhibit Growth of Pseudomonas aeruginosa." Antimicrob Agents Chemother, 2019;63(9). PMID: 31262758.
- [pubmed] Talà A, et al. "Thiostrepton, a resurging drug inhibiting the stringent response to counteract antibiotic-resistance and expression of virulence determinants in Neisseria gonorrhoeae." Front Microbiol, 2023;14:1104454. PMID: 36910221.
- [pubmed] McConkey GA, et al. "Inhibition of Plasmodium falciparum protein synthesis. Targeting the plastid-like organelle with thiostrepton." J Biol Chem, 1997;272(4):2046-9. PMID: 8999899.
- [pubmed] Kwok JM, et al. "Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression." Mol Cancer Ther, 2008;7(7):2022-32. PMID: 18645012.
- [pubmed] Hegde NS, et al. "The transcription factor FOXM1 is a cellular target of the natural product thiostrepton." Nat Chem, 2011;3(9):725-31. PMID: 21860463.
- [pubmed] Newick K, et al. "Peroxiredoxin 3 is a redox-dependent target of thiostrepton in malignant mesothelioma cells." PLoS One, 2012;7(6):e39404. PMID: 22761781.
- [pubmed] Su G, et al. "Thiostrepton as a Potential Therapeutic Agent for Hepatocellular Carcinoma." Int J Mol Sci, 2024;25(17). PMID: 39273665.
- [pubmed] Chen M, et al. "Thiostrepton induces oxidative stress, mitochondrial dysfunction and ferroptosis in HaCaT cells." Cell Signal, 2024;121:111285. PMID: 38969192.
- [pubmed] Kim TH, et al. "Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection." Molecules, 2019;24(24). PMID: 31835481.
- [pubmed] Wang M, et al. "Micelle-encapsulated thiostrepton as an effective nanomedicine for inhibiting tumor growth and for suppressing FOXM1 in human xenografts." Mol Cancer Ther, 2011;10(12):2287-97. PMID: 21903609.
- [pubmed] Lai CY, et al. "Identification of Thiostrepton as a Novel Inhibitor for Psoriasis-like Inflammation Induced by TLR7-9." J Immunol, 2015;195(8):3912-21. PMID: 26371257.
- [pubmed] Luo Y, et al. "Thiostrepton alleviates experimental colitis by promoting RORγt ubiquitination and modulating dysbiosis." Cell Mol Immunol, 2023;20(11):1352-1366. PMID: 37752225.
- [pubmed] Esparza K, et al. "Thiostrepton-Nanomedicine, a TLR9 Inhibitor, Attenuates Sepsis-Induced Inflammation in Mice." Mediators Inflamm, 2023;2023:4035516. PMID: 37662481.
- [pubmed] Jin P, et al. "The Clinical and Experimental Research on the Treatment of Endometriosis with Thiostrepton." Anticancer Agents Med Chem, 2019;19(3):323-329. PMID: 29308746.
- [clinical-trial] Gibson V, et al. "Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer." Nat Commun, 2026;17(1). PMID: 42448681.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Veterinary status comes from the eCFR text of 21 CFR 524.1600a and 524.1600b, and human status from Drugs@FDA (openFDA) and EMA's Article 57 product data, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.