Halofuginone
Halofuginone (febrifugine derivative, prolyl-tRNA synthetase inhibitor)
Written by Aaron CuhaReviewed Sep 2026
Also known as: Tempostatin, HT-100, Halocur (veterinary), Febrifugine derivative, RU-19110
Extended male mouse median lifespan by 8.8 percent in the 2021 Interventions Testing Program cohort, one of the larger single-cohort male effects the programme has reported, with no effect in females. In people it has only ever been given in a 24-patient oncology phase 1 where nausea limited dosing, small topical studies, and a Duchenne programme that was terminated.
Overview
Halofuginone is a synthetic derivative of febrifugine, the active alkaloid of the Chinese herb Dichroa febrifuga. It is used as a veterinary antiprotozoal, and in the 2000s it was developed as an oral anti-fibrotic and anti-angiogenic cancer drug under the name tempostatin, then as HT-100 for Duchenne muscular dystrophy. Neither programme produced an approved human medicine, and no halofuginone product for humans appears in the FDA's approved drug database.
The human record is small. In a European phase 1, 24 patients with advanced solid tumours received 106 courses at 0.5 to 3.5 mg a day by mouth. The acute maximum tolerated dose was 3.5 mg a day, limited by nausea, vomiting and fatigue, and the recommended dose for chronic use was 0.5 mg a day with anti-emetic cover. Several patients had bleeding complications in which a causal role could not be excluded. A phase 2 of topical halofuginone in AIDS-related Kaposi sarcoma found reduced type I collagen in treated lesions but too few evaluable patients to assess efficacy. A single patient with chronic graft-versus-host disease improved on topical treatment in 1999. The Duchenne programme (HT-100) enrolled 17 boys in a phase 1b and ran two extension studies; all three registry records are TERMINATED with the reason given as "dosing stopped" and no results posted.
In mice, the NIA Interventions Testing Program fed halofuginone from 7 months of age. Male median lifespan rose from 794 to 864 days, an 8.8 percent increase (log-rank p = 0.002), and survival to the 90th percentile age rose 6.9 percent (Wang-Allison p = 0.01). Females showed no change (median +0.2 percent, p = 0.75). The paper's main text does not state the diet concentration; it is in the supplementary tables. Separately, a 2025 study reported that halofuginone caused weight loss in diet-induced obese mice and in pigs by raising GDF15 and FGF21 through the integrated stress response.
Mechanism of action
Halofuginone binds glutamyl-prolyl-tRNA synthetase and inhibits its prolyl-tRNA synthetase activity, which is reversed by adding proline. That triggers the amino acid starvation response, an arm of the integrated stress response, and in mouse and human T cells in culture it selectively blocks Th17 differentiation. Its older description as an inhibitor of type I collagen synthesis is a downstream consequence of the same mechanism. The ITP selected it because amino acid restriction extends lifespan in several species and halofuginone pharmacologically mimics that signal. In humans the only mechanistic data are that topical application lowered collagen alpha1(I) gene expression in skin biopsies from one graft-versus-host patient and type I collagen in Kaposi sarcoma lesions, and that plasma levels were undetectable after topical use. The 2025 report that it suppresses food intake and raises GDF15 and FGF21 is in mice and pigs; nothing equivalent has been measured in a person.
Human evidence
Very little. Halofuginone has been given orally to 24 cancer patients in one phase 1, topically in one small Kaposi sarcoma trial and one graft-versus-host case report, and orally to 17 boys with Duchenne muscular dystrophy in a programme that was terminated without published results. No healthy volunteer has received it in a published study and no study has measured any ageing endpoint.
- Oral phase 1, 24 patients with advanced solid tumours: 0.5 to 3.5 mg a day; nausea, vomiting and fatigue defined the ceiling at 3.5 mg a day; 0.5 mg a day with anti-emetics was the recommended chronic dose; several bleeding events of uncertain causality.
- Topical phase 2 in AIDS-related Kaposi sarcoma: reduced type I collagen in treated lesions; efficacy not assessable because too few participants could be evaluated.
- Single graft-versus-host patient treated topically for 6 months: reduced skin collagen synthesis and improved neck rotation, reversed on stopping; plasma levels undetectable.
- Duchenne (HT-100): phase 1b in 17 boys plus two extension studies, all recorded as terminated with "dosing stopped" as the reason and no results posted. A registered trial that stopped and never reported is itself a finding.
- No published study has given halofuginone to a healthy adult, and none has looked for any effect related to ageing.
What this does not tell you: Nothing here shows benefit in a person for any indication. The oral dose people tolerated chronically (0.5 mg a day) was set by nausea and vomiting, and the phase 1 recorded bleeding events. Whether the mouse dose that extended lifespan corresponds to anything a person could take is unknown. The Duchenne termination is unexplained in the public record.
Reading the research record
The NIA Interventions Testing Program runs each compound in parallel at three sites (The Jackson Laboratory, the University of Michigan and UT Health San Antonio) in genetically heterogeneous UM-HET3 mice, tests both sexes, analyses them separately, pools the sites in a site-stratified log-rank test, and publishes every result whether or not the compound worked. It is publicly funded by the National Institute on Aging with no pharmaceutical sponsorship. In the 2021 cohort halofuginone produced an 8.8 percent increase in male median lifespan (p = 0.002) and a 6.9 percent increase in 90th percentile survival, and nothing in females. In the same cohort the male result was the strongest of the three positives by p value, and the effect on late survival is the part that distinguishes a candidate geroprotector from a compound that only prevents early deaths. It has been tested once, at one dose and start age.
The reason nobody knows what it does in people is that both human programmes stopped. Tempostatin's oral development did not proceed past the phase 1 that found the chronic dose limited to 0.5 mg a day by nausea. The Duchenne programme changed hands between three small companies and ended with all three registry records terminated and unreported; the public record gives "dosing stopped" and nothing more, so the reason cannot be stated here. Halofuginone is an old molecule with veterinary generics, so there is no exclusivity to pay for a new human programme, and without one the mouse result will stay a mouse result. That cuts both ways: the absence of trials is not evidence it fails in people, and it equally leaves any harm unmeasured.
The evidence, charted
Fig. 1 · evidence composition
4of 8 citations (50%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 8 distinct years, 1999 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Animal2026
Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice
Interventions Testing Program 2021 cohort, treatment from 7 months. Male median lifespan 864 versus 794 days (+8.8 percent, log-rank p = 0.002), 90th percentile survival +6.9 percent (p = 0.01); 154 treated males against 298 controls. Females: median +0.2 percent, p = 0.75. NIA funded.
GeroScience - Human2006
Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumours
24 patients, 106 courses, 0.5 to 3.5 mg a day by mouth. Acute maximum tolerated dose 3.5 mg a day (nausea, vomiting, fatigue); recommended chronic dose 0.5 mg a day with 5-HT3 antagonists. Several patients had bleeding complications in which causality could not be excluded. Linear pharmacokinetics with large between-patient variability. EORTC study.
European Journal of Cancer - Human2011
Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma
Blinded intrapatient vehicle-controlled topical study. Type I collagen fell significantly only in halofuginone-treated lesions; MMP-2 unchanged. Too few evaluable participants to assess efficacy. NCI-supported consortium trial.
Journal of Acquired Immune Deficiency Syndromes - Human1999
Topical treatment of cutaneous chronic graft versus host disease with halofuginone: a novel inhibitor of collagen type I synthesis
One patient. Daily ointment on one side of the neck for 6 months reduced skin collagen synthesis and improved neck rotation on the treated side; effects reversed after stopping. No plasma halofuginone detectable. A single case, not a trial.
Transplantation - Human2016
Safety, tolerability and pharmacokinetics of single and multiple doses of HT-100 in Duchenne muscular dystrophy
Phase 1b, 17 boys enrolled, sponsor Processa Pharmaceuticals (earlier Halo Therapeutics and Akashi). Status TERMINATED, reason recorded as "dosing stopped". No results posted. Two extension studies (NCT01978366, NCT02525302) are also terminated without results.
ClinicalTrials.gov - In vitro2012
Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase
Identified glutamyl-prolyl-tRNA synthetase as the molecular target; inhibition reversed by exogenous proline. Explains the anti-fibrotic, anti-inflammatory and anti-malarial activities of the febrifugine family through one mechanism.
Nature Chemical Biology - In vitro2009
Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response
Selectively blocked mouse and human Th17 differentiation in culture via the amino acid starvation response, rescued by excess amino acids, and protected mice from experimental autoimmune encephalomyelitis. Cell and mouse data.
Science - Animal2025
The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21
In diet-induced obese mice and in pigs, halofuginone suppressed food intake, raised energy expenditure and produced weight loss via integrated stress response induction of FGF21 and GDF15; both hormones were required in knockout mice. Animal only. Note that the abstract describes halofuginone as FDA-approved for scleroderma, which the FDA approved drugs database does not support.
Science Advances
Frequently asked questions
What did the ITP find for halofuginone?
In male mice fed from 7 months of age, median lifespan rose 8.8 percent (864 versus 794 days, p = 0.002) and survival to the 90th percentile age rose 6.9 percent, pooled across three sites. Female mice showed no change. It has been tested in one cohort only.
Has halofuginone been given to people?
Yes, but rarely. 24 cancer patients took it by mouth in a phase 1, where nausea and vomiting limited the long-term dose to 0.5 mg a day and some patients had bleeding complications. Small topical studies exist in Kaposi sarcoma and one graft-versus-host patient. A Duchenne muscular dystrophy programme in 17 boys was terminated and never reported results.
Is halofuginone approved anywhere for humans?
No. It is a veterinary antiprotozoal. The FDA approved drugs database lists no halofuginone product, and neither of the human development programmes reached approval. A 2025 paper's description of it as FDA-approved for scleroderma is not supported by that database.
How does it work?
It inhibits prolyl-tRNA synthetase, which switches on the amino acid starvation response. In cell culture that blocks Th17 differentiation and collagen synthesis; in mice and pigs it raises GDF15 and FGF21 and causes weight loss. The ITP chose it as a drug mimic of amino acid restriction. None of this has been measured in a person beyond skin collagen in biopsies.