{"id":71515,"date":"2026-05-20T10:40:00","date_gmt":"2026-05-20T10:40:00","guid":{"rendered":"https:\/\/medsbase.com\/foxo4-dri\/"},"modified":"2026-05-21T07:14:08","modified_gmt":"2026-05-21T07:14:08","slug":"foxo4-dri","status":"publish","type":"product","link":"https:\/\/medsbase.com\/el\/foxo4-dri\/","title":{"rendered":"FOXO4-DRI (FOX04-DRI) \u2014 \u03a0\u03b5\u03c0\u03c4\u03b9\u03b4\u03b9\u03ba\u03ae \u0388\u03c1\u03b5\u03c5\u03bd\u03b1 \u03a3\u03b5\u03bd\u03bf\u03bb\u03c5\u03c4\u03b9\u03ba\u03ae\u03c2 \u0394\u03c1\u03ac\u03c3\u03b7\u03c2"},"content":{"rendered":"

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Quick Answer \u2014 What is FOXO4-DRI?<\/h3>\n

FOXO4-DRI<\/strong> (also written FOX04-DRI; “DRI” = D-Retro-Inverso) is a synthetic ~28-amino-acid senolytic peptide<\/strong> developed by Baar, Brandt, de Keizer, Demaria, Campisi and colleagues at the Erasmus University Medical Center, and published in the landmark Cell<\/em> paper “Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging” (Baar et al., March 2017). The peptide is the D-amino-acid retro-inverso version of a FOXO4 transactivation-domain fragment (corresponding to residues ~86\u2013100 of human FOXO4). Sequence in conventional reading order: LTLRKEPASEIAQSILEAYSQNGWANRRSAGGNTPS<\/strong> (all D-amino acids, retro-inverso orientation; MW ~3,000 Da). Mechanism: FOXO4 normally tethers p53 to the nucleus of senescent cells, allowing them to evade apoptosis despite active p53 signalling. FOXO4-DRI competitively binds p53’s transactivation domain, displaces native FOXO4, and frees p53 to translocate to mitochondria \u2014 triggering selective senolysis<\/strong> (apoptosis of senescent cells only). Landmark “exercise-of-senescence” research compound. For laboratory research use only.<\/p>\n<\/div>\n

\u0391\u03c5\u03c4\u03cc \u03c0\u03bf\u03c5 \u03bb\u03b1\u03bc\u03b2\u03ac\u03bd\u03b5\u03c4\u03b5 \u03bc\u03b5 \u03c4\u03b7\u03bd MedsBase:<\/strong> Lyophilized \u226599% HPLC-verified FOXO4-DRI \u00b7 COA available on request \u00b7 Discreet temperature-stable packaging \u00b7 Worldwide research-supply courier \u00b7 1,400+ verified \u03ba\u03c1\u03b9\u03c4\u03b9\u03ba\u03ad\u03c2 \u03c0\u03b5\u03bb\u03b1\u03c4\u03ce\u03bd<\/a><\/div>\n

\ud83d\udce6 \u039a\u03ac\u03b8\u03b5 \u03c0\u03b1\u03c1\u03b1\u03b3\u03b3\u03b5\u03bb\u03af\u03b1 \u03ba\u03b1\u03bb\u03cd\u03c0\u03c4\u03b5\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03a0\u03bf\u03bb\u03b9\u03c4\u03b9\u03ba\u03ae \u0395\u03b3\u03b3\u03cd\u03b7\u03c3\u03b7\u03c2 \u0395\u03c0\u03b1\u03bd\u03b1\u03c0\u03bf\u03c3\u03c4\u03bf\u03bb\u03ae\u03c2<\/strong><\/a> \u2014 \u03b5\u03ac\u03bd \u03c4\u03bf \u03b4\u03ad\u03bc\u03b1 \u03c3\u03b1\u03c2 \u03b4\u03b5\u03bd \u03c6\u03c4\u03ac\u03c3\u03b5\u03b9 \u03b5\u03bd\u03c4\u03cc\u03c2 20 \u03b5\u03c1\u03b3\u03ac\u03c3\u03b9\u03bc\u03c9\u03bd \u03b7\u03bc\u03b5\u03c1\u03ce\u03bd, \u03c4\u03bf \u03b5\u03c0\u03b1\u03bd\u03b1\u03c0\u03bf\u03c3\u03c4\u03ad\u03bb\u03bb\u03bf\u03c5\u03bc\u03b5.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\u03a0\u03c1\u03bf\u03b4\u03b9\u03b1\u03b3\u03c1\u03b1\u03c6\u03ae<\/th>\n\u039b\u03b5\u03c0\u03c4\u03bf\u03bc\u03ad\u03c1\u03b5\u03b9\u03b1<\/th>\n<\/tr>\n<\/thead>\n
Compound Class<\/strong><\/td>\nSynthetic ~28-aa D-amino-acid retro-inverso peptide; senolytic compound; p53-FOXO4 protein-protein interaction inhibitor<\/td>\n<\/tr>\n
Chemical Name<\/strong><\/td>\nFOXO4-DRI (alternative spellings: FOX04-DRI; FOXO4-D-Retro-Inverso; Baar\/Demaria\/de Keizer senolytic peptide; ProxoFen \u2014 earlier preclinical name)<\/td>\n<\/tr>\n
\u0391\u03c1\u03b9\u03b8\u03bc\u03cc\u03c2 CAS<\/strong><\/td>\nResearch-grade peptide \u2014 no widely-registered single CAS; identification by published sequence (Baar et al. 2017) and supplier COA<\/td>\n<\/tr>\n
Sequence (forward reading)<\/strong><\/td>\nLTLRKEPASEIAQSILEAYSQNGWANRRSAGGNTPS (forward reading order; all 28 residues in D-amino-acid stereochemistry<\/strong>, retro-inverso orientation relative to native L-FOXO4 sequence). Some published variants use a slightly different fragment length \/ residue range; consult COA for batch-specific sequence.<\/td>\n<\/tr>\n
\u039c\u03bf\u03c1\u03b9\u03b1\u03ba\u03cc \u0392\u03ac\u03c1\u03bf\u03c2<\/strong><\/td>\n~3,000 Da (varies slightly by published sequence variant)<\/td>\n<\/tr>\n
\u039c\u03bf\u03c1\u03b9\u03b1\u03ba\u03cc\u03c2 \u03a4\u03cd\u03c0\u03bf\u03c2<\/strong><\/td>\nD-retro-inverso peptide \u2014 sequence-derived approximate MF C105<\/sub>H184<\/sub>N30<\/sub>O27<\/sub>; published MW ~2,330 Da. Exact formula varies slightly across supplier batches because the canonical Baar 2017 sequence has been replicated by multiple groups with minor cell-penetrating-peptide linker variants.<\/td>\n<\/tr>\n
Mechanism<\/strong><\/td>\nIn senescent cells, native FOXO4 binds the p53 transactivation domain and tethers p53 in the nucleus \u2014 preventing p53 from triggering apoptosis despite the cellular damage that activated p53 in the first place. This is part of why senescent cells survive and accumulate with ageing. FOXO4-DRI<\/strong> mimics the FOXO4-binding interface to p53 but in inverse-stereochemistry retro-inverso orientation \u2014 it competitively occupies the p53 binding site, displaces native FOXO4, and frees p53. The released p53 translocates to mitochondria where it triggers intrinsic apoptosis<\/strong> via the p53-mediated Bax \/ Bak \/ cytochrome-c-release cascade. Selective for senescent cells because they have both (a) FOXO4-tethered p53 and (b) activated p53 already; non-senescent cells have neither and are unaffected.<\/td>\n<\/tr>\n
D-Amino-Acid Stereochemistry<\/strong><\/td>\nThe retro-inverso D-amino-acid design confers protease-resistance \u2014 host proteases recognise only L-amino acids \u2014 extending in-vivo half-life and enabling oral \/ IP dosing in published rodent protocols.<\/td>\n<\/tr>\n
Published In-Vivo Effects (Baar 2017)<\/strong><\/td>\nSelective clearance of senescent cells from aged mice; restoration of fur density and quality; restoration of physical fitness \/ running endurance; restoration of renal function biomarkers; improvement in DOX-induced senescence-mediated injury models. The paper produced one of the most-cited demonstrations that senescent-cell clearance can functionally rejuvenate aged organisms.<\/td>\n<\/tr>\n
Form \/ Purity \/ Storage<\/strong><\/td>\nLyophilized white-to-off-white powder, \u226599% HPLC. Store 2\u20138 \u00b0C short-term, \u221220 \u00b0C long-term. Reconstituted: 2\u20138 \u00b0C, use within 30 days. Avoid freeze-thaw.<\/td>\n<\/tr>\n
\u0395\u03c1\u03b5\u03c5\u03bd\u03b7\u03c4\u03b9\u03ba\u03ae \u03a7\u03c1\u03ae\u03c3\u03b7<\/strong><\/td>\nFor laboratory research use only. Not on the WADA Prohibited List. Preclinical research compound. No formal human clinical trials of FOXO4-DRI itself; related senolytic compounds (dasatinib + quercetin, fisetin, navitoclax) are in clinical-translational research separately.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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Mechanism of Action \u2014 Selective Senolysis via p53-FOXO4 Disruption<\/h2>\n

FOXO4-DRI is the canonical research-tool example of peptide-based senolytic pharmacology<\/strong>. The senolytic concept (selectively killing senescent cells without affecting normal cells) is one of the most-cited current frameworks for anti-ageing therapeutics. FOXO4-DRI’s mechanistic story is unusually clean:<\/p>\n