Pharmaceuticals

Dasatinib + Quercetin (Senolytic Stack)

Evidence: moderate_human

Mechanism of Action

Dasatinib is a multi-kinase inhibitor (targeting SRC, ABL, c-KIT, PDGFR, and ephrin receptors) originally developed for chronic myeloid leukemia. Quercetin is a natural flavonoid that inhibits PI3K, serpine/PAI-2, BCL-xL, and other anti-apoptotic pathways. Together, they constitute a senolytic combination that selectively induces apoptosis in senescent cells by disabling the senescent cell anti-apoptotic pathways (SCAPs) that allow damaged, non-dividing cells to resist programmed cell death. Senescent cells accumulate with aging and secrete the SASP (senescence-associated secretory phenotype) — inflammatory cytokines, matrix metalloproteinases, and growth factors that drive tissue dysfunction. By clearing senescent cells, D+Q reduces SASP-driven chronic inflammation.

Dosing Protocol

Standard: Research indicates Dasatinib 100 mg + Quercetin 1000-1250 mg orally for 2 consecutive days, repeated every 2-4 weeks (intermittent 'hit-and-run' dosing).

Maintenance: Research indicates the same 2-day intermittent protocol every 2-4 weeks. Some protocols use monthly 3-day courses.

Administration: oral

Timing: Take both compounds together on dosing days, with or without food. The 'hit-and-run' approach exploits the fact that senolytic effect occurs rapidly but senescent cells take weeks to re-accumulate. Quercetin bioavailability is improved by fat co-ingestion.

Duration: Ongoing intermittent cycles. Long-term safety data in healthy populations is limited. Typically used in periodic courses (e.g., 2 days per month for 3-6 months, then reassess).

Notes

The dasatinib + quercetin senolytic combination was first demonstrated by Kirkland et al. at Mayo Clinic. The 2019 pilot study in diabetic kidney disease (NCT02848131) showed decreased senescent cell markers, reduced SASP, and improved physical function after just 3 days of treatment. CRITICAL: This is a 'hit-and-run' protocol — intermittent dosing only. Continuous dasatinib at oncology doses causes significant hematologic toxicity. Required bloodwork: CBC with differential and platelets (before and 7-10 days after each course), CMP, liver function panel, coagulation panel. Chest X-ray or echocardiogram if pulmonary symptoms develop. Senescence biomarkers (p16INK4a, SASP panel) where available for efficacy monitoring. Medical supervision required.

Stacking

  • Fisetin (complementary senolytic)
  • Rapamycin (reduces senescent cell formation upstream)
  • Spermidine (autophagy induction)
  • NAD+ precursors (NMN/NR — cellular energy support)

Interactions

  • Anticoagulants (Warfarin) [HIGH] — Dasatinib causes thrombocytopenia and increases bleeding risk. Quercetin may inhibit CYP2C9, potentiating warfarin.
  • CYP3A4 inhibitors/inducers [MEDIUM] — Dasatinib is a CYP3A4 substrate. Inhibitors (ketoconazole, grapefruit) increase levels; inducers (rifampin) decrease levels.
  • Proton pump inhibitors / H2 blockers [MEDIUM] — Dasatinib absorption requires gastric acidity. PPIs reduce dasatinib exposure by 60%. Use antacids separated by 2 hours.
  • Antihypertensives [MEDIUM] — Dasatinib can cause fluid retention and pulmonary arterial hypertension. Monitor blood pressure.

Contraindications

  • Active bleeding disorders or thrombocytopenia
  • Severe hepatic impairment
  • Pulmonary arterial hypertension
  • QT prolongation risk or concurrent QT-prolonging drugs
  • Pregnancy and breastfeeding
  • Active infections (temporary immunosuppression)

Side Effects

  • GI discomfort, nausea, diarrhea (both compounds)
  • Fluid retention and peripheral edema (dasatinib)
  • Headache
  • Thrombocytopenia and neutropenia (dasatinib — typically mild at senolytic doses)
  • Pleural effusion (rare at intermittent dosing; more common with chronic oncology dosing)
  • Skin rash

Key Papers

  • 10.1016/j.ebiom.2019.08.069
  • 10.1038/s41591-018-0092-9
  • 10.1016/j.ebiom.2023.104481

Source Quality

Dasatinib: FDA-approved pharmaceutical (Sprycel) for CML — used off-label for senolytic purpose. Requires prescription. Quercetin: OTC dietary supplement — use phytosome/lipophilic formulation for bioavailability (e.g., Quercefit). Ensure pharmaceutical-grade dasatinib.

Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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