Screening for
Inhibitors of Bcl-2-IP3R Interaction. Lead
Investigator: Clark W. Distelhorst,
Case Western Reserve School of Medicine.
The Foundation has awarded a grant to Case Western Reserve University to
fund research supervised by Dr. Clark W. Distelhorst, M.D. Dr. Distelhorst, and other researchers
working with him, are investigating a means to prevent the Bcl-2 protein from
inhibiting the death of CLL cells.
The Bcl-2 protein is produced by the Bcl-2 gene and promotes the
proliferation of CLL cells by interfering with their death. This fact reduces the effectiveness of
drug treatments for CLL and for other Bcl-2 positive malignancies such as
lymphomas.
Dr. Distelhorst and his team are investigating the interaction between
the Bcl-2 protein and a calcium channel receptor. They have developed a decoy peptide that
binds to the Bcl-2 protein, disrupts the interaction between the protein and the
receptor, and promotes the death of CLL cells. The funds provided by the Foundation
will enable Dr. Distelhorst to investigate thirty-nine drug like compounds to
determine whether the compounds induce the death of CLL cells by disrupting the
interaction between the Bcl-2 protein and the calcium channel receptor. Compounds that are found to do so will
be considered for development as drugs and for further testing.