Discovery of Peptides with Anti-Proliferative Effects
2003-10-20 07:30 (New York)
Publications Describe Technology with Broad Application for Drug Discovery in
Various Therapeutic Areas
SOUTH SAN FRANCISCO, Calif., Oct. 20 /PRNewswire-FirstCall/ -- Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced that it has discovered
peptides with anti-proliferative activity from a functional screen using
retroviral-delivered random peptide libraries. The results appeared in two
related scientific papers co-authored by Rigel researchers published in the
October issue of the peer-reviewed journal, Chemistry & Biology. The peptides
discovered are novel and exhibited dose-dependent anti-proliferative effects
on tumor cells while showing no signs of cytotoxicity -- precisely the peptide
characteristics the screen was designed to discover.
Broad Applicability
Rigel believes that its technology as described in these publications is
broadly applicable to many diseases. The ability to discover peptides that
alter or improve disease processes, such as proliferation in cancer, can
facilitate the development of novel therapeutics. Most diseases can be
modeled using functional assays with relevant read-outs, such as
proliferation. Large, diverse peptide libraries can be screened in these
assays in a high-throughput manner. Those peptides that are found to alter
the disease process, such as preventing proliferation, may have therapeutic
utility either as a peptide drug itself or as a starting point for small
molecule drug discovery. In addition to cancer, Rigel has used this technology
to initiate drug discovery in inflammatory diseases such as allergy and asthma
and is currently applying it to Hepatitis C.
"The creation of diverse peptide libraries and subsequent analysis of
their effects is a powerful tool for manipulating disease processes in a
cellular context and for the discovery of drugs," said Dr. Donald G. Payan,
Chief Scientific Officer and Executive Vice President of Rigel. "This
technology has proven valuable in numerous therapeutic research applications."
Technology Coalescence
These papers outline the coalescence of a large number of key
technologies, which allow this type of screening to occur. These technologies
include large random diverse peptide library generation, retroviral technology
to deliver these peptides into the cell, reporter proteins to identify markers
of interest, inducible expression systems to regulate the intracellular
expression of these peptides, high throughput FACS analysis, mass spec to
identify interacting proteins and the creation of functional assays to model
diseases. Rigel has been a pioneer in the creation of intracellular small
cyclic peptide libraries, which are more stable than linear peptides and, as a
result, offer a better opportunity for drug discovery (see Journal of
Biological Chemistry, Vol. 227, No. 40, Kinsella, et al.). Rigel has
industrialized these technologies, incorporating them into a cohesive and
functional system, which, as these publications illustrate, may have an
important role in the discovery of novel therapeutics.
Full text of the papers can be obtained at: www.chembiol.com
Cellular Localization and Antiproliferative Effect of Peptides Discovered
from a Functional Screen of a Retrovirally Delivered Peptide Library
Yasumichi Hitoshi, Tarikere Gururaja, Denise M. Pearsall, Wayne Lang,
Poonam Sharma, Betty Huang, Susan M. Catalano, John McLaughlin, Erlina Pali,
Beau Peele, Jorge Vialard, Michel Janicot, Walter Wouters, Walter Luyten, Mark
K. Bennett, Dave C. Anderson, Donald G. Payan, James B. Lorens, Jacob
Bogenberger and Susan Demo.
Cellular Interacting Proteins of Functional Screen-derived
Antiproliferative and Cytototoxic Peptides Discovered using Mass Spectrometry
Based Shotgun Peptide Sequencing
Tarikere Gururaja, Weiquin Li, Susan Catalano, Jacob Bogenberger, Jing
Zheng, Bernd Keller, Jorge Vialard, Michel Janicot, Liang Li, Yashumichi
Hitoshi, Donald G. Payan and D. C. Anderson.
About Rigel (www.rigel.com)
Rigel's mission is to become a source of novel, small-molecule drugs to
meet large, unmet medical needs. Rigel has identified three lead product
development programs: mast cell inhibition to treat immunologic diseases such
as asthma/allergy and autoimmune disorders, antiviral agents to treat
hepatitis C, and ligases a new class of cancer drug targets. Rigel has begun
clinical testing of its first product candidate, R112, for allergic rhinitis,
and it plans to begin clinical trials of three additional drug candidates, for
the treatment of hepatitis C, rheumatoid arthritis and asthma by the end of
2004. |
