FOXO4-DRI

Designed by Baar and colleagues and published in Cell in 2017. Its front half mimics part of the FOXO4 protein, and its back half is a reversed HIV-TAT sequence that carries it into cells. The developer is Cleara Biotech.

In aged (senescent) cells, the FOXO4 protein binds p53 and keeps those damaged cells alive. FOXO4-DRI competes for that link, which in cell studies pushed p53 out of the nucleus and triggered programmed cell death. Clearing senescent cells is meant to reduce the inflammatory signals they release.

In cell culture it was about 11.7 times more potent against senescent lung cells than normal ones. In mice it reversed chemotherapy-related weight loss and liver-enzyme rises, and improved fur density, fitness and kidney markers in fast-aging and naturally aged mice, with highly variable responses. A 2020 mouse study reported higher testosterone and fewer senescence markers in aged testes. No human trial, case series or pharmacokinetic study has been published, so nothing is known about its effects or safety in people.

No human safety data exists. The original authors advise against long-term FOXO4 suppression because it interferes with p53 and DNA-damage repair, and mouse researchers flagged possible muscle and heart toxicity as untested. Immune reactions to a large synthetic peptide with a viral segment have not been studied.

Not FDA-approved and no human trial has been registered. It is not eligible for compounding: no USP monograph and not on FDA's 503A nominations list (May 2026). As an unapproved substance it falls under WADA's S0 category, prohibited at all times. Status as of October 2026.