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Can I read A Cell Type Selective YM155 Prodrug Targets Receptor-Interacting Protein Kinase 2 to Induce Brain Cancer Cell Death on EtoBox?
A Cell Type Selective YM155 Prodrug Targets Receptor-Interacting Protein Kinase 2 to Induce Brain Cancer Cell Death by Thomas J. West; Junfeng Bi; Francisco Martínez-Peña; Ellis J. Curtis; Nathalia R. Gazaniga; Paul S. Mischel; Luke L. Lairson is a Chemistry article available to read on EtoBox.
What is A Cell Type Selective YM155 Prodrug Targets Receptor-Interacting Protein Kinase 2 to Induce Brain Cancer Cell Death about?
Glioblastoma (GBM) is the most prevalent and aggressive primary central nervous system (CNS) malignancy. YM155 is a highly potent broad-spectrum anti-cancer drug that was derived from a phenotypic screen for functional inhibitors of survivin expression, but for which the relevant biomolecular target remains unknown. Presumably as a result of its lack of cell-type selectivity, YM155 has suffered from tolerability issues in the clinic. Based on its structural similarity to the GBM-selective prodrug RIPGBM, here, we report the design, synthesis, and characterization of a prodrug form of YM155, termed aYM155. aYM155 displays potent cell killing activity against a broad panel of patientderived GBM cancer stem-like cells (IC 50 = 0.7−10 nM), as well as EGFR-amplified and EGFR variant III-expressing (EGFRvIII) cell lines (IC 50 = 3.8−36 nM), and becomes activated in a cell-type-dependent manner. Mass spectrometry-based analysis indicates that enhanced cell-type selectivity results from relative rates of prodrug activation in transformed versus non-transformed cell types. The prodrug strategy also facilitates transport into the brain (brain-to-plasma ratio, aYM155 = 0.56; YM155 = BLQ). In
Who reads A Cell Type Selective YM155 Prodrug Targets Receptor-Interacting Protein Kinase 2 to Induce Brain Cancer Cell Death?
It is typically read by researchers, students, and practitioners in Chemistry.
- Author
- Thomas J. West; Junfeng Bi; Francisco Martínez-Peña; Ellis J. Curtis; Nathalia R. Gazaniga; Paul S. Mischel; Luke L. Lairson
- Publisher
- American Chemical Society (ACS)
- Published
- 2023
- Language
- EN
- Field
- Chemistry (Physical Sciences)