{"id":"foxo4-dri","name":"FOXO4-DRI","aliases":["FOXO4 D-retro-inverso peptide","senolytic peptide","Proxofim"],"url":"https://lyoresearch.com/compounds/foxo4-dri","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"FOXO4-DRI is a cell-penetrating peptide designed to pry the protein FOXO4 away from p53 inside senescent cells, causing those cells to die. In a 2017 Cell paper it restored fitness, fur density and kidney function in aged and prematurely ageing mice. That is the entire evidence base: no human trial, no human safety data, and no regulatory filing. Products sold under the name are unlicensed research chemicals.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0","regulatory_status":"Not approved (preclinical)","molecule":{"formula":"C228H388N86O64","molecular_weight":"5358","cas":"2460055-10-9","pubchem_cid":167312269,"note":"Record is the TFA salt form"},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Any outcome in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0","evidence":"No clinical study is registered or published. LYO's search found none.","references":[{"citation":"PubMed and ClinicalTrials.gov search: FOXO4-DRI — no human study identified.","where":"Searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=FOXO4-DRI+clinical"}]},{"outcome":"Fitness, fur density and renal function (aged mice)","grade":"D","grade_meaning":"no human evidence","effect_size":"large","adverse":false,"human_studies":"Animal only","evidence":"Baar and colleagues report selective clearance of senescent cells and functional restoration in fast-ageing and naturally aged mice, and protection against chemotherapy toxicity.","references":[{"citation":"Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging.","where":"Cell, 2017;169:132–147","url":"https://pubmed.ncbi.nlm.nih.gov/28340339/"}]},{"outcome":"Senescent cell clearance (human cells in vitro)","grade":"D","grade_meaning":"no human evidence","effect_size":"moderate","adverse":false,"human_studies":"Cell culture","evidence":"Removed senescent cells from expanded human chondrocytes in a 2021 study — the closest the compound has come to a human tissue.","references":[{"citation":"Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes.","where":"Front Bioeng Biotechnol, 2021","url":"https://pubmed.ncbi.nlm.nih.gov/33996787/"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"Preclinical; supply for human use is unlawful."},{"region":"United States","status":"Not approved","note":"Not FDA-approved; no IND announced."},{"region":"United Kingdom","status":"Not licensed","note":"Unlicensed."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved, so S0 (non-approved substances)."}],"faq":[{"q":"Has FOXO4-DRI been tested in humans?","a":"No. Not one trial, at any phase. The evidence is mice and cell culture."},{"q":"Is FOXO4-DRI a senolytic?","a":"In mice, yes — it selectively killed senescent cells. Whether it does so safely in people is unknown."},{"q":"Why is it sold if untested?","a":"Because the mouse paper was widely reported and the sequence is public. Availability online says nothing about safety or legality; it is an unapproved substance everywhere."}],"references":[{"cite":"Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging.","where":"Cell, 2017;169:132–147","url":"https://pubmed.ncbi.nlm.nih.gov/28340339/","note":"Mice."},{"cite":"PubMed and ClinicalTrials.gov search: FOXO4-DRI — no human study identified.","where":"Searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=FOXO4-DRI+clinical"},{"cite":"Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes.","where":"Front Bioeng Biotechnol, 2021","url":"https://pubmed.ncbi.nlm.nih.gov/33996787/","note":"Human cells in culture."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade D: no human study."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}