concept

Dasatinib

Also known as: D

Facts (10)

Sources

Cellular rejuvenation: molecular mechanisms and potential ... - Nature nature.com Nature Mar 14, 2023 10 facts

measurementA clinical trial (NCT02848131) suggested that senolytics using a combination of Dasatinib and Quercetin (D + Q) improved physical function in patients with chronic kidney disease (CKD).

claimDasatinib (D), quercetin (Q), and fisetin (F) were chosen for senolytic study because they have established safety profiles or FDA approval for other human purposes, facilitating a faster transition from research to clinical application.

measurementIn vivo experiments in senescent cell-transplanted young mice and naturally aged mice showed that intermittent oral administration of Dasatinib plus quercetin alleviated physical dysfunction, reduced mortality hazard to 65%, and increased post-treatment survival by 36%.

referenceDasatinib is used as a second-line treatment or in newly diagnosed chronic phase chronic myeloid leukemia patients, according to Zhu et al. in BioDrugs (2011).

claimGenetic elimination of p16 improves age-related osteoporosis, and a combination of Dasatinib (D) and Quercetin (Q) repairs bone microstructure in radiation-related osteoporosis.

claimIn obese mice, the combination of Dasatinib and Quercetin (D + Q) reduces circulating inflammatory mediators, increases insulin sensitivity, boosts glucose tolerance, and promotes adipogenesis.

claimThe combination of Dasatinib and Quercetin (D + Q) for treating osteoporosis is currently being evaluated in clinical trial NCT04313634.

claimThe combination of Dasatinib and quercetin can eliminate senescent mesenchymal embryonic fibroblasts from Ercc1−/− mice and bone marrow mesenchymal progenitors from old mice, whereas either drug alone is ineffective.

claimSenescent human pre-adipocytes or mesenchymal stem cells (MSCs) are susceptible to Dasatinib but not quercetin or fisetin, whereas senescent human umbilical vein endothelial cells (HUVECs) are susceptible to quercetin or fisetin but not Dasatinib.

claimDasatinib triggers apoptosis in senescent cells by blocking Src kinase, which interferes with dependency receptors like ephrins.