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Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.
- Source :
-
FEBS letters [FEBS Lett] 2017 Jan; Vol. 591 (1), pp. 240-251. Date of Electronic Publication: 2016 Dec 19. - Publication Year :
- 2017
-
Abstract
- Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors.<br />Pdb Id Codes: Comp. 2: 5IEZ; Comp. 5: 5IF4.<br /> (© 2016 Federation of European Biochemical Societies.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Bcl-2-Like Protein 11 metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Drug Design
Drug Discovery
Humans
Immunoprecipitation
Membrane Potential, Mitochondrial drug effects
Mice
Myeloid Cell Leukemia Sequence 1 Protein metabolism
bcl-X Protein metabolism
Antineoplastic Agents pharmacology
Myeloid Cell Leukemia Sequence 1 Protein antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3468
- Volume :
- 591
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Editorial & Opinion
- Accession number :
- 27878989
- Full Text :
- https://doi.org/10.1002/1873-3468.12497