Dasatinib — BCR-ABL/Src kinase inhibitor — FDA-approved tyrosine kinase inhibitor (CML/ALL) with investigational senolytic off-label use
Dasatinib is a potent second-generation BCR-ABL/Src/Lck/Yes/PDGFR tyrosine kinase inhibitor FDA-approved for CML and Ph+ ALL. Its senolytic activity was discovered by Kirkland and colleagues at Mayo Clinic (2015): (1) Dasatinib selectively eliminates senescent pre-adipocytes (but NOT senescent endothelial cells) by inhibiting pro-survival kinases (PDGFR, src-family kinases) that senescent cells upregulate to evade apoptosis — the Senescent Cell Anti-Apoptotic Pathways (SCAPs); (2) Quercetin (the combination partner) eliminates senescent endothelial cells and other cell types by inhibiting PI3K/AKT and Bcl-xl; (3) The D+Q combination is complementary — targeting different senescent cell populations. CRITICAL CONTEXT: Dasatinib doses used for senolytic therapy (100 mg single dose, repeated every 3–6 months) are the SAME as CML doses — this means senolytic protocols carry ALL the cardiovascular and toxicity risks of cancer chemotherapy.
نظرة عامة
هذه الصفحة جزء من مكتبة المركّبات المُصنَّفة بالأدلة في Hormonaly. جميع الادعاءات السريرية مرتبطة بمصادر علمية مُحكَّمة عبر خط أنابيب التحقق المزدوج للاستشهادات.
فئة المركّب
BCR-ABL/Src kinase inhibitor — FDA-approved tyrosine kinase inhibitor (CML/ALL) with investigational senolytic off-label use
آلية العمل
Dasatinib is a potent second-generation BCR-ABL/Src/Lck/Yes/PDGFR tyrosine kinase inhibitor FDA-approved for CML and Ph+ ALL. Its senolytic activity was discovered by Kirkland and colleagues at Mayo Clinic (2015): (1) Dasatinib selectively eliminates senescent pre-adipocytes (but NOT senescent endothelial cells) by inhibiting pro-survival kinases (PDGFR, src-family kinases) that senescent cells upregulate to evade apoptosis — the Senescent Cell Anti-Apoptotic Pathways (SCAPs); (2) Quercetin (the combination partner) eliminates senescent endothelial cells and other cell types by inhibiting PI3K/AKT and Bcl-xl; (3) The D+Q combination is complementary — targeting different senescent cell populations. CRITICAL CONTEXT: Dasatinib doses used for senolytic therapy (100 mg single dose, repeated every 3–6 months) are the SAME as CML doses — this means senolytic protocols carry ALL the cardiovascular and toxicity risks of cancer chemotherapy.
الوضع التنظيمي
FDA APPROVED for CML and Ph+ ALL at 70–140 mg/day. All senolytic use is OFF-LABEL. No FDA approval for aging/senescence. Off-label senolytic use must be supervised by a physician experienced with oncological drug toxicity.
مستوى الأدلة
C — Phase 1 first-in-human senolytic trial (Hickson et al. 2019, n=9 IPF): confirmed reduction in senescent cell burden. Phase 2 completed for IPF (NCT02715518). Phase 2 trials ongoing for Alzheimer's (UNKEPT, NCT04785300) and diabetic kidney disease. No Phase 3 senolytic data as of 2024. All senolytic dosing carries the FULL toxicity profile of a second-generation TKI.