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Mol Med Rep. 2019 Jun;19(6):5053-5062. doi: 10.3892/mmr.2019.10209. Epub 2019 Apr 30.

Perspectives of small molecule inhibitors of activin receptor‑like kinase in anti‑tumor treatment and stem cell differentiation (Review).

Author information

1
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
2
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract

Activin receptor‑like kinases (ALKs), members of the type I activin receptor family, belong to the serine/threonine kinase receptors of the transforming growth factor‑β (TGF‑β) superfamily. ALKs mediate the roles of activin/TGF‑β in a wide variety of physiological and pathological processes, ranging from cell differentiation and proliferation to apoptosis. For example, the activities of ALKs are associated with an advanced tumor stage in prostate cancer and the chondrogenic differentiation of mesenchymal stem cells. Therefore, potent and selective small molecule inhibitors of ALKs would not only aid in investigating the function of activin/TGF‑β, but also in developing treatments for these diseases via the disruption of activin/TGF‑β. In recent studies, several ALK inhibitors, including LY‑2157299, SB‑431542 and A‑83‑01, have been identified and have been confirmed to affect stem cell differentiation and tumor progression in animal models. This review discusses the therapeutic perspective of small molecule inhibitors of ALKs as drug targets in tumor and stem cells.

PMID:
31059090
DOI:
10.3892/mmr.2019.10209

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