Maternal embryonic leucine zipper kinase (MELK) functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis.

An overview of MELK

Maternal embryonic leucine zipper kinase (MELK), a member of the snf1/AMPK family of protein serine/threonine kinases, is a regulator of intracellular signaling that closely relates to a variety of cellular and biological processes including cell cycle, proliferation, apoptosis, hematopoiesis and oncogenesis. MELK is confirmed to be involved in tumorigenic processes for the overexpression of MELK in different cancers and oncogenic interaction between MELK and numerous proteins. At present, studies on the function of MELK mainly focus on cell cycle regulation, embryo development regulation and the role in oncogenesis. MELK consists of catalytic domain, UBA-domain, TP-rich domain, KA1-domain, and ATP binding region.

Inhibition of MELK

Clinically, MELK is an important target for prognosis assessment on patients with brain tumors and development of anti-tumor drugs. BEKE et al found that the proliferation of MELK was conducted by promoting DNA damage tolerance. Therefore, targeting MELK to inhibit catalytic activity and stability of proteins is a promising way to make tumors sensitive to DNA damage agents. OTSSP167, an effective inhibitor of MELK, has been used in phase I clinical trials in solid tumors. So far, there is no inhibitor of MELK approved by FDA for clinical use, but an increasing number of MELK inhibitors have been studied in recent years, which may be attributed to the complex factors involved in the development of tumors and the function and mechanism of MELK in oncogenesis that have been not clarified.


Figure 1 Schematic representation of current targets for inhibition of MELK protein synthesis and kinase activity


MELK and diseases

The MELK gene is carcinogenic and highly expressed in malignant epithelial tumor in digestive tract, lung, ovarian, breast, and skin. The expression level of MELK is associated with prognosis and drug resistance. Experiments show that MELK gene deficiency can inhibit the growth of tumor in vivo and vitro. Thus, MELK is an attractive target for the treatment of tumors.


1. Jiang, P. & Zhang, D. Maternal Embryonic Leucine Zipper Kinase (MELK): A Novel Regulator in Cell Cycle Control, Embryonic Development, and Cancer. International Journal of Molecular Sciences 14, 21551-21560 (2013).

2. Li, S. et al. Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in gastric cancer. Oncotarget 7, 6266-6280 (2016).

3. Cao, L. S. et al. Structural basis for the regulation of maternal embryonic leucine zipper kinase. PLoS One 8, e70031 (2013).

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