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Chemical dissection of the cell cycle: probes for cell biology and anti-cancer drug development
- Source :
- Cell death & disease, vol 5, iss 10, Cell Death & Disease, Senese, S; Lo, YC; Huang, D; Zangle, TA; Gholkar, AA; Robert, L; et al.(2014). Chemical dissection of the cell cycle: Probes for cell biology and anti-cancer drug development. Cell Death and Disease, 5(10). doi: 10.1038/cddis.2014.420. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1h90z1bq
- Publication Year :
- 2014
- Publisher :
- eScholarship, University of California, 2014.
-
Abstract
- Cancer cell proliferation relies on the ability of cancer cells to grow, transition through the cell cycle, and divide. To identify novel chemical probes for dissecting the mechanisms governing cell cycle progression and cell division, and for developing new anti-cancer therapeutics, we developed and performed a novel cancer cell-based high-throughput chemical screen for cell cycle modulators. This approach identified novel G1, S, G2, and M-phase specific inhibitors with drug-like properties and diverse chemotypes likely targeting a broad array of processes. We further characterized the M-phase inhibitors and highlight the most potent M-phase inhibitor MI-181, which targets tubulin, inhibits tubulin polymerization, activates the spindle assembly checkpoint, arrests cells in mitosis, and triggers a fast apoptotic cell death. Importantly, MI-181 has broad anti-cancer activity, especially against BRAFV600E melanomas.
- Subjects :
- Cancer Research
Programmed cell death
M Phase Cell Cycle Checkpoints
Cell division
1.1 Normal biological development and functioning
Immunology
Oncology and Carcinogenesis
Mitosis
Antineoplastic Agents
Polymerization
Small Molecule Libraries
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Underpinning research
Tubulin
Neoplasms
Drug Discovery
Genetics
Humans
030304 developmental biology
Cancer
0303 health sciences
biology
Cell Death
Cell Cycle
Cell Biology
Cell cycle
3. Good health
Cell biology
High-Throughput Screening Assays
Spindle checkpoint
Phenotype
5.1 Pharmaceuticals
030220 oncology & carcinogenesis
Hela Cells
Molecular Probes
Cancer cell
biology.protein
Original Article
Biochemistry and Cell Biology
Development of treatments and therapeutic interventions
HeLa Cells
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell death & disease, vol 5, iss 10, Cell Death & Disease, Senese, S; Lo, YC; Huang, D; Zangle, TA; Gholkar, AA; Robert, L; et al.(2014). Chemical dissection of the cell cycle: Probes for cell biology and anti-cancer drug development. Cell Death and Disease, 5(10). doi: 10.1038/cddis.2014.420. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1h90z1bq
- Accession number :
- edsair.doi.dedup.....891351dd949a80a49ae29d1c6d7dd45a