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Discovery and biological characterization of potent myeloid cell leukemia‐1 inhibitors

Journal Article · · FEBS Letters
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  1. Department of Biochemistry Vanderbilt University School of Medicine Nashville TN USA
  2. Department of Hematology and Medical Oncology and The Winship Cancer Institute Emory University Atlanta GA USA
  3. Department of Cell and Molecular Biology St. Jude Children's Research Hospital Memphis TN USA
  4. Vanderbilt University Medical Center Nashville TN USA
  5. Department of Adult Oncology The Dana‐Farber Cancer Institute Harvard Medical School Boston MA USA
+ Show Author Affiliations

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 RNA i 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.

PDB ID codes

Comp. 2 : 5IEZ ; Comp. 5 : 5IF4 .

Sponsoring Organization:
USDOE
OSTI ID:
1399279
Alternate ID(s):
OSTI ID: 1419082
Journal Information:
FEBS Letters, Journal Name: FEBS Letters Journal Issue: 1 Vol. 591; ISSN 0014-5793
Publisher:
Wiley Blackwell (John Wiley & Sons)Copyright Statement
Country of Publication:
Netherlands
Language:
English

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