Recent Patents on Biotechnology

Nikolaos Labrou
Laboratory of Enzyme Technology, Department of Biotechnology
Agricultural University of Athens Iera Odos 75, Gr-118 55


Recent Inventions on Receptor Tyrosine Kinase RET Modulation

Author(s): Adrian Goldman and Jaana M. Jurvansuu

Affiliation: Structural Biology and Biophysics, Institute of Biotechnology, Biocenter 3, University of Helsinki,Viikinkaari 1, FIN-00014, Helsinki, Finland.


Rearranged during transfection, RET, is a receptor tyrosine kinase expressed in neural crest derived cell lineages. RET is activated by dimerisation facilitated by its binding to the heterodimeric complex formed by Glial cell-derived neurotrophic factor (GDNF) -family ligand (GFL) and GNDF-family receptor (GFR). Both GDNFs and their co-receptors are a small protein family of four members. RET kinase mediated signaling can lead to survival, cell growth, differentiation, and migration. Pharmaceutically RET is of interest due to its involvement in several disease conditions. Oncogenic RET activation by mutations or rearragements predisposes to cancers like multiple endocrine neoplasia type 2 (A and B) and medullary thyroid carcinoma. Loss-of-function mutations in RET are a strong susceptibility factor for Hirschsprung disease, which is characterized by lack of ganglion cells in gastrointestinal tract. All the GFLs promote neuronal survival and GDNF is one of the most potent neurotrophic factors for dopaminergic neurons. Therefore, the neuroprotective capacity of RET activation to override the apoptotic program in neurodegenerative diseases, like in dying midbrain dopaminergic neurons in Parkinsons disease, is of great interest. This article reviews the recent international patents on modulation of RET kinase activity by small-molecule and peptide-based agonists and antagonists.

Keywords: RET, GDNF-family ligands, GDNF-family receptors, small-molecule kinase inhibitors, Gas1, Gral

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Article Details

Page: [47 - 54]
Pages: 8
DOI: 10.2174/187220808783330910