46-residue D-retro-inverso peptide. 2025 NMR confirms it binds p53 N-terminal transactivation domain (TAD2, Kd ~400 nM), competing out FOXO4-p53 interaction and triggering selective apoptosis of senescent cells.
No approved use. Research-use reagent only. No human clinical trials completed or registered.
No human clinical data. PK/ADME, serum half-life, immunogenicity unspecified.
Discovery paper (Cell 2017). Multiple independent preclinical studies across tissues. 2025 NMR structural clarification. Improved analog CL04183 nominated as development candidate.
- 1.Baar et al., Cell 2017 — selective apoptosis of senescent cells, restoration of tissue homeostasis after doxorubicin and in aged mice. Discovery/Preclinical
- 2.Nature Communications 2025 — p53 TAD2 binding confirmed by NMR. Kd 400 +/- 280 nM. Corrects earlier framing to 'binds p53 TAD2'. Structural
- 3.Aging 2020 — FOXO4-DRI in aged Leydig cell model: improved testicular microenvironment. Preclinical
- 4.Frontiers 2021 — senolytic activity in expanded human chondrocytes. Preclinical
- 5.US20230090099A1 Patent — CL04183 improved selectivity/potency vs FOXO4-DRI. Preclinical
No human clinical trials. Reproducibility concern: 2020 paper reports '25 mM' for Leydig cells — likely unit error. No formal CMC or regulatory review.
Cleara Biotech advancing CL04183 toward Phase 1a/1b (claimed 2026+). 2025 NMR structural paper sharpened mechanism.