Class: Drug (selective tyrosine kinase receptor inhibitor that is prescribed for certain types of leukemia)
Alias(es): CAS# 302962-49-8; Trade names: Sprycel; Dasanix
Background: Dasatinib, sold under the brand names Sprycel and Dasanix, is a synthetic medication available by prescription only, that has been FDA approved since 2006, and is currently approved for treating chronic Philadelphia chromosome-positive (Ph+) myeloid leukemia in both adults and children[2,3]. Dasatinib has shown specificity for clearing senescent cells of certain types, i.e. preadipocytes (progenitor fat cells that have hormonal, metabolic, and pro-inflammatory functions) both in vitro in human cells and in vivo in mice and rats. There are no results yet for clinical studies involving dasatinib for treating aging in humans, but preclinical studies involving the combination of dasatinib and another senolytic, quercetin, (D+Q) to target a broader range of senescent cells have shown promising results in terms of extending healthspan and lifespan and ameliorating age-related dysfunctions (see preclinical studies section).
Is there evidence it works in humans for aging?
Is there evidence it works in preclinical studies for aging?
Dasatinib + Quercetin (D+Q) preclinical studies: Benefits of D+Q for aging (as demonstrated in preclinical studies) include reduction of senescent cell burden and inflammatory markers, and improvements in cardiovascular health, gut microbiome, fatty liver disease, bone health and disc degeneration, strength and physical health, and cognitive health. See table below for references and details.
The figure above is from a review by Martel et al., 2020. It shows the pathways inhibited by senolytic supplements, such as Quercetin, and drugs, such as Dasatinib, that lead to reduced viability of senescent cells and/or apoptosis of senescent cells.
Dasatinib (D) is a synthetic src-tyrosine kinase inhibitor, and has been found to be senolytic against human pre-adipocytes without affecting non-senescent cells. D promotes apoptosis of senescent cells by targeting Src family tyrosine kinases, (i.e. BCR/ABL, Src, c-Kit, ephrin), which are known to be Senescent Cell Anti-Apoptotic Pathway (SCAP) components, a pro-survival network utilized by senescent cells to avoid apoptosis. The senolytic activity of D reduces levels of Senescence-Associated Secretory Phenotype (SASP), an inflammatory and damaging property of senescent cells. D is commonly used in combination with quercetin (Q), a flavonoid senolytic that targets senescent endothelial cells, to achieve a broader senolytic effect than when either are used alone.
Are there known safety concerns?
In a 2018 human study involving treating idiopathic pulmonary fibrosis (IPF) patients (ages 55-84) with intermittent DQ (D:100 mg/day, Q:1250 mg/day, three-days/week over three-weeks), all patients were retained for the study course with no D+Q discontinuation. Although there was no placebo arm, the adverse events reported were consistent with previous placebo arms in trials for IPF, and there was only one serious adverse event (pneumonia and edema) which was completely resolved after hospitalization. There were no changes in laboratory tests to indicate any liver or kidney toxicity and pulmonary function did not change.
The drug label for SPRYCEL describes known side effects of use for dasatinib, although it is limited mainly to use in cancer patients: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021986s7s8lbl.pdf
3. Research, C. for D. E. and. (2019). FDA approves dasatinib for pediatric patients with CML. FDA. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-dasatinib-pediatric-patients-cml
5. Song, S., Tchkonia, T., Jiang, J., Kirkland, J. L., & Sun, Y. (2020). Targeting Senescent Cells for a Healthier Aging: Challenges and Opportunities. Advanced Science, 7(23), 2002611. https://doi.org/10.1002/advs.202002611
6. Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., O’Hara, S. P., LaRusso, N. F., Miller, J. D., Roos, C. M., Verzosa, G. C., LeBrasseur, N. K., Wren, J. D., Farr, J. N., Khosla, S., … Kirkland, J. L. (2015). The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell, 14(4), 644–658. https://doi.org/10.1111/acel.12344