Category: pharmacological
Aliases: ABT-263
BH3-mimetic Bcl-2 / Bcl-xL inhibitor — induces apoptosis in senescent cells (senolytic). Major dose-limiting platelet drop from Bcl-xL on megakaryocytes. Original oncology indications largely abandoned for venetoclax (Bcl-2 selective); senolytic research interest persists. PK (Wilson Lancet Oncol 2010 Phase I PMID:21282543 + lymphatic-transport PK PMID:24212376): Low aqueous solubility, high logP — F ~30% in humans (56.5% in fed dogs, lower in fasted state — strong food effect). Apparent Vd ~0.5–0.7 L/kg (~35–50 L), t½ 22.2 h, Tmax 5–6 h (slow absorption via mixed portal + lymphatic uptake). Exposure dose-proportional 50–425 mg/d. Phase I dose-limiting toxicity was thrombocytopenia (Bcl-xL on-target effect on platelets), which paved the way for the more Bcl-2-selective venetoclax (Venclexta).
PO: 22.2h