Gossypol (AT-101, Cottonseed Polyphenol)

Gossypol/AT-101 pan-inhibits Bcl-2/Bcl-xL/Mcl-1 (BH3-like) for Bax/Bak release/apoptosis ↑, + VEGF/NF-κB/PI3K ↓ for angio/survival curb. Phase I/II modest in prostate/NSCLC/CLL; 20–60 mg PO safe but tox-limited—combo potential with RT/chemo.

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Human-reviewed · How we review →

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👥⭐⭐⭐ Moderate — Strong mechanistic and preclinical data; early-phase clinical trials with AT-101 show safety but limited efficacy as monotherapy. Potential in combination regimens still under study.AT-101(-)-GossypolCottonseed Gossypol

Forms: Oral capsules (Rx/investigational, 20–60 mg)

Educational only, not medical advice. OncoForge makes no claim that Gossypol (AT-101, Cottonseed Polyphenol) treats, prevents, or cures any condition, beyond what the linked studies show. Evidence levels vary; effects may not translate to people, and some compounds can cause harm. Always coordinate with your oncology team.

Key Takeaway

A pan–Bcl-2 family (BH3-mimetic–like) natural product that can free up apoptosis machinery and modestly inhibit angiogenesis; the (-)-enantiomer AT-101 has human trial data with limited monotherapy efficacy but potential in combinations.

Evidence at a glance

Tier 3 · early humanProstateNon-Small Cell LungHead/NeckLymphoid (CLL)

Moderate clinical (phase I/II safety/efficacy signals) + robust preclinical; combos underexplored.

How it may work

Gossypol is a natural polyphenolic aldehyde from cottonseed that functions as a pan–Bcl-2 family inhibitor (‘BH3 mimetic’). By binding to anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1), it frees pro-apoptotic Bax/Bak, leading to mitochondrial outer-membrane permeabilization, cytochrome c release, and caspase activation. It also suppresses angiogenesis (VEGF ↓), disrupts NF-κB and PI3K/AKT signaling, and can radiosensitize or chemosensitize resistant tumors. The synthetic (-)-enantiomer AT-101 has been tested clinically in prostate, lung, head/neck, and lymphoid malignancies, but with modest responses.

Targets & pathways

Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.

Bcl-2/Bcl-xL/Mcl-1↓Pan-BH3 mimetic; frees Bax/Bak for MOMP
Apoptosis↑Cytochrome c release, caspase activation
VEGF↓Inhibits angiogenesis/endothelial proliferation
NF-κB/PI3K/AKT↓Disrupts survival/inflammatory signaling

Bcl-2Mcl-1ApoptosisAngiogenesis

Often studied / combined with

Combinations reported in the literature, not a protocol or a recommendation.

Docetaxel / Chemotherapy: Apoptosis boost in NSCLC.
Radiotherapy: Sensitization via NF-κB in head/neck.

Overlapping mechanisms

Bcl-2 ↓ / Apoptosis ↑: Avoid with other BH3 mimetics (e.g., venetoclax); risk thrombocytopenia/GI overload.

Safety & interactions

Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.

Risk categories

Gi Upset ModerateFatigue ModerateHepatotoxicity Risk MildInfertility ReversibleHypokalemia RiskPregnancy Avoid

Potential interactions

Potassium-depleting diuretics (e.g., furosemide)MonitorModerateTheoreticalExacerbates hypokalemia.
Chemotherapy (e.g., docetaxel) / RadiotherapyConsiderBeneficialTheoreticalSensitization via apoptosis/NF-κB in prostate/NSCLC.
Bcl-2 inhibitors (e.g., venetoclax)MonitorModerateTheoreticalOverlapping targets; potential additive tox.

Timing

With food: Reduces GI upset.
Daily or cycled: E.g., 21 days on/7 off; BID for higher doses.
Monitor LFTs/electrolytes: Weekly initially, then biweekly.

References

Research

No published studies for Gossypol (AT-101, Cottonseed Polyphenol) yet

New studies appear here once they’ve been reviewed. Browse all studies.

Dose: as studied, not a recommendation

These are doses as studied or reported, never a recommendation. The right amount of Gossypol (AT-101, Cottonseed Polyphenol) depends on you, your other medicines, and your situation; decide it with your oncology team and pharmacist, not from a web page.

Ranges seen in adjunct / practice use: 20–60 mg (po) AT-101 trials: 20 mg/day continuous or 30–60 mg/day (e.g., 30 mg BID) in cycles. Phase II prostate: 30 mg/day x5/7 days. Preclinical HED from mouse (10–50 mg/kg) ~0.8–4 mg/kg (~56–280 mg for 70 kg); clinical capped lower due to tox., Rx/investigational only. Titrate from 20 mg; monitor LFTs weekly. Cycles (e.g., 21 on/7 off) to manage fatigue/GI. Potassium supplementation if hypokalemia. Strict MD oversight..

Trials studying Gossypol (AT-101, Cottonseed Polyphenol)

No actively-recruiting trials matched right now. Recruiting is not the same as proven. Search ClinicalTrials.gov →

Inclusion here is not an endorsement. OncoForge makes no claim beyond what the linked studies show. Discuss anything on this page with your oncology team before acting on it.

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