Publication Details (including relevant citation information):
Author(s): Nikolovska-Coleska Z, Bajwa N, Liu M, et al.
Conference Information: 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, NOV 16-19, 2010 Berlin, GERMANY
Source: EJC SUPPLEMENTS Volume: 8 Issue: 7 Pages: 94-94 Published: NOV 2010
Times Cited: 0
The anti-apoptotic myeloid cell leukemia protein Mcl-1, a member of the Bcl-2 family proteins, has emerged as a promising therapeutic target. It was demonstrated that Mcl-1 is an important survival factor for pancreatic cancer cells; its down-regulation with siRNA for example, enhances the induction of apoptosis, chemosenstivity and radiosenstivity of pancreatic cancer cells. Therefore targeting Mcl-1 to overcome apoptosis resistance is an important strategy for the development of new drugs to treat pancreatic cancer. Through high throughput screening approach we have identified several promising lead compounds which bind to the BH3 binding site in Mcl-1 selectively over Bcl-2 and Bcl-xL, and distrupt interactions between analogues and established initial structure-activity relationships. Collectively, these findings provide good promise for further chemical modifications of this compound and further optimization toward developing a new class of anticancer drugs, Mcl-1 inhibitors.
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