Navitoclax (ABT-263)

BH3 mimetic that inhibits the BCL-2, BCL-XL, and BCL-W anti-apoptotic proteins. Displaces pro-apoptotic BH3-only proteins (BIM, BAD) from their sequestration by BCL-2 family members, triggering mitochondrial outer membrane permeabilization and caspase-dependent apoptosis in senescent cells that rely on BCL-2/BCL-XL for survival. Potent senolytic but dose-limited by on-target thrombocytopenia due to platelet dependence on BCL-XL.

Half-life

8 hours

Bioavailability

~50% (oral, estimated from Phase I data)

Route

oral

Evidence tier

T3 — Community / emerging

Optimization pillars

anti-aging · cellular-health

References

4 peer-reviewed

Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative

50 mg single dose

Experimental senolytic (research only)

moderate

150 mg for 1-2 days/month

Intermittent senolytic cycling (investigational)

aggressive

250–325 mg/day continuous

Oncologic dose (clinical trials only)

Monitoring

wbc
rbc
hemoglobin
hematocrit
alt
ast
bilirubin
creatinine
lipid-panel

Contraindications

thrombocytopenia
active-bleeding-disorder
concurrent-anticoagulants
concurrent-strong-cyp3a4-inhibitors
pregnancy

References

PMID:26822237An old age-associated p53 target gene, PCDH7, in skin aging — Aging Cell, 2016
PMID:27013615Clearance of senescent cells by ABT-263 rejuvenates hematopoietic stem cells in mice — Nat Med, 2016
PMID:31575608Navitoclax as a senolytic in age-related pathologies — Trends Pharmacol Sci, 2019
PMID:33328614BCL-2 family inhibitors as senolytics — Cell Metab, 2020

Notes

Navitoclax is the most potent senolytic identified to date and the one you should not be taking outside a clinical trial. The BCL-2/BCL-XL inhibition mechanism is clean in theory — senescent cells depend on these anti-apoptotic proteins for survival, knock them out and the zombie cells die. The problem is platelets also depend on BCL-XL. Dose-dependent thrombocytopenia is not a side effect. It is a pharmacological certainty. The research value is enormous. The self-experimentation risk is unacceptable. Evidence tier 3 for longevity applications because the human safety data outside oncology does not yet exist.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

See Navitoclax (ABT-263) in a protocol matched to you