💊 Senolytic Combination Dasatinib Quercetin Simulator

Two Drugs, Two Senescent Anti-Apoptotic Pathways

Dasatinib and quercetin hit different survival nodes senescent cells rely on.

• Src/BCR-ABL: Dasatinib target (tyrosine kinase inhibitor)
• BCL-2/PI3K: Quercetin target (flavonoid, multi-pathway)
• SCAP disruption: Combined mechanism (senescent cell anti-apoptotic pathway)
• Senescent > normal: Selectivity (apoptosis bias in target cells)

Why two drugs instead of one

Placeholder: senescent cells use redundant survival pathways requiring dual blockade.

Placeholder callout: neither drug alone clears senescent cells as efficiently as the pair.

Hit-and-Run: Why D+Q Is Dosed in Short Pulses

A brief high-exposure pulse clears senescent cells without continuous drug exposure.

• 2–3 days: Typical pulse length (per treatment cycle)
• 2–4 weeks: Typical interval (drug-free between pulses)
• Hit-and-run: Rationale (transient exposure, lasting effect)
• Minimized: Toxicity goal (vs. chronic daily dosing)

The pulse-and-rest logic

Placeholder: senolytics need only transient exposure to trigger apoptosis, unlike senostatics.

Placeholder callout: intermittent dosing schedule reduces cumulative drug burden.

The Clearance Window: Senescent Cells Undergo Apoptosis

During the pulse, senescent cells lose anti-apoptotic protection and die selectively.

• 0–72 hrs: Peak clearance window (post-pulse)
• ~30–60%: Senescent cell drop (in preclinical models)
• IL-6, IL-8 ↓: SASP factor decline (reduced inflammatory secretion)
• Minimal: Healthy cell impact (selective apoptosis)

What happens during the clearance pulse

Placeholder: dual pathway blockade tips senescent cells into apoptosis within days.

Placeholder callout: clearance is transient and requires repeated pulses.

The Drug-Free Interval: Tissue Remodeling and Repopulation

Between pulses, debris clears and healthy cells repopulate the tissue niche.

• 1–4 weeks: Recovery window (between pulses)
• Macrophage-mediated: Debris clearance (efferocytosis of dead cells)
• Gradual: Reaccumulation risk (senescent cells slowly return)
• Scheduled: Next pulse trigger (fixed interval protocol)

Why rest periods matter

Placeholder: recovery intervals let normal tissue repair before the next pulse.

Placeholder callout: reaccumulation of senescent cells motivates repeat pulsing.

Measuring Success: Trial Endpoints for D+Q Therapy

Clinical trials track physical function, biomarkers, and frailty over repeated cycles.

• Physical function: Primary endpoint (gait speed, chair-stand test)
• SASP panel: Biomarker endpoint (circulating inflammatory markers)
• Phase 2: Trial phase (2026) (multiple indications)
• 3–12: Dosing cycles studied (per trial protocol)

What trials actually measure

Placeholder: outcome measures combine function, biomarkers, and safety across cycles.

Placeholder callout: cumulative benefit may require multiple pulse cycles to detect.