Description:
Apoptosis or
programmed cell death is an essential process in the development and homeostasis
of all multi-cellular organisms such as humans. Suppression of programmed cell
death is a contributing reason for a range of human diseases such as
cancer. Thus finding a strategy to specifically down-regulate the
functions of Bcl-2 and Bcl-xL is important to potential anti-cancer
therapies.
Past effort in
screening and designing Bcl-2/Bcl-xL inhibitors has been rather primitive, in
part because there was an absence of a general code or principle that governs
the interaction among Bcl-2 family members. Researchers at Princeton University,
in Molecular Biology, have determined the three dimensional structure of
CED-9 (a Bcl-2 homologue) in complex with a functional EGL-1 fragment
(encompassing the BH3 region). These structural studies, for the first
time, allow for the derivation of such Code, which will greatly facilitate the
design of specific compounds that can discriminate against some members (such as
Bax and Bak) of the Bcl-2 family while retaining specific and high affinity
binding for other members (such as Bcl-xL and Bcl-2). This will greatly improve
the specificity of such compounds in treating cancer cells and help in
minimizing potential side effects.
Princeton is
currently seeking industrial collaboration to commercialize this technology.
Patent protection is pending.
Publications
Yan,N., Gu,L., Kokel,D., Chai,,J.,
Li,W., Han,A., Chen,l., Xue,D., Shi,Y., September 2004, Structural, Biochemical,
and Functional Analyses of CED-9 Recognition by the Proapoptotic Proteins EGL-1
and CED-4, Molecular Cell, Vol. 15, 1-10.
For more information on Princeton
University invention # 05-2159 please contact:
Laurie Tzodikov
Office of Technology Licensing and Intellectual Property
Princeton University
4 New South Building
Princeton, NJ 08544-0036
(609) 258-7256
(609) 258-1159 fax
tzodikov@princeton.edu