TrkC-Targeted Kinase Inhibitors And PROTACs. Academic Article

abstract

• A small molecule motif (IY-IY), which binds the tropomyosin receptor kinase C (TrkC), was used to deliver the promiscuous kinase inhibitor (KI) dasatinib into breast cancer. Conjugates with noncleavable (1) and cleavable (2) linkers were compared in cellular assays and shown to have more impact on the cell viabilities of TrkC+ breast cancer cells over TrkC- epithelial cells. The IY-IY fragment was also used to recruit the E3 ligase cereblon, giving a potent proteolysis targeting chimeric (PROTAC) for TrkC degradation in metastatic breast cancer cells.

authors

• Burgess, Kevin

published proceedings

• Mol Pharm

altmetric score

• 0.5

author list (cited authors)

• Zhao, B., & Burgess, K.

citation count

• 14

complete list of authors

• Zhao, Bosheng||Burgess, Kevin

publication date

• October 2019

publisher

• American Chemical Society (ACS)  Publisher

published in

• Molecular Pharmaceutics  Journal

keywords

• Active Targeting
• Adaptor Proteins, Signal Transducing
• Breast Neoplasms
• Cell Survival
• Chemotherapy
• Dasatinib
• Female
• Humans
• Protacs
• Proteasome Endopeptidase Complex
• Protein Kinase Inhibitors
• Proteolysis
• Receptor, Trkc
• Small Molecule Libraries
• Triple Negative Breast Cancer Cells
• Trkc Receptors
• Tumor Cells, Cultured
• Ubiquitin-Protein Ligases
• Wound Healing

PubMed Central ID

• 31512882

Digital Object Identifier (DOI)

• 10.1021/acs.molpharmaceut.9b00673

start page

• 4313

end page

• 4318

volume

• 16

issue

• 10

URL

• http://dx.doi.org/10.1021/acs.molpharmaceut.9b00673