PA-457 is the First in a New Class of Antiretrovirals Called
Maturation Inhibitors
GAITHERSBURG, Md., Oct. 21 /PRNewswire/ -- Panacos Pharmaceuticals today
announced the publication of a study elucidating the mechanism of action of
its lead drug candidate, PA-457, in development for the treatment of Human
Immunodeficiency Virus (HIV) infection. Panacos researchers, working in
collaboration with scientists at the National Institute of Allergy and
Infectious Diseases (Bethesda, MD) and The George Washington University
Medical Center (Washington, DC), demonstrated that PA-457 disrupts viral
maturation, the final step in the HIV life cycle. Maturation involves the
processing of the HIV capsid protein, which is required for the formation of a
functional core structure within the virus. PA-457 blocks capsid processing
so that virus particles released from treated cells have a defective core
structure, are non-infectious and therefore cannot spread the infection to
other cells. PA-457 is the first compound known to target this step in virus
replication. The discovery is described in a paper appearing this week in the
online edition of the Proceedings of the National Academy of Sciences of the
USA.
"The most pressing need in HIV treatment today is for new therapies that
are effective against drug resistant strains of the virus," said Carl Wild,
Ph.D., Panacos' Chief Science Officer. "Panacos' strategy for tackling this
problem is to develop drugs that attack HIV at different points in its life
cycle from those targeted by existing drugs. Our work demonstrates that,
unlike currently approved antiretroviral drugs, PA-457 interferes with the
assembly of the capsid shell surrounding the virus's nucleic acid core.
Consistent with this observation, PA-457 potently inhibits virus strains
resistant to approved HIV drugs. These findings suggest that PA-457 may one
day provide a new treatment option for the increasing number of patients
infected by drug resistant strains of HIV."
Ongoing preclinical studies with PA-457 indicate that the compound is
orally bioavailable in animals, resulting in plasma concentrations that are
likely to be therapeutic if achieved in man. PA-457 is synergistic in action
with approved HIV drugs when tested in vitro, an important characteristic
since the compound would likely be used in combination with drugs that act at
other points in the virus life cycle. Furthermore, in vitro metabolism
studies suggest that PA-457 is unlikely to cause clinically significant drug-
drug interactions with other antiretroviral agents. Preclinical testing on
PA-457 should be completed in the near future, enabling the Company to file an
IND application in order to initiate human clinical testing of the drug
candidate.
Graham Allaway, Ph.D., President and CEO of Panacos commented: "Our
findings show that PA-457 is the first in an entirely new class of
antiretrovirals called Maturation Inhibitors. Panacos is now in the unique
position of having identified both a novel HIV therapeutic target and a lead
compound against this target that has suitable properties for further
development. The Company is moving aggressively to advance PA-457 into
clinical trials. At the same time we are expanding our drug discovery efforts
to identify second generation Maturation Inhibitors."
Panacos Pharmaceuticals is a privately held company engaged in the
discovery and development of small molecule, orally available drugs for the
treatment of HIV infection and other major human viral diseases. Its
proprietary discovery technologies focus on novel targets in the virus life
cycle, including the first and last steps of virus infection, namely fusion of
virus to human cells and virus maturation.
The publication, co-authored with Ritu Goila-Gaur, Ph.D. and Eric O.
Freed, Ph.D. of the National Institutes of Health and Jan Marc Orenstein,
M.D., Ph.D. of The George Washington University Medical Center, can be located
at http://www.pnas.org/cgi/doi/10.1073/pnas.2234683100.
More information on Panacos Pharmaceuticals is available on its website:
http://www.panacos.com or by contacting info@panacos.com.
SOURCE Panacos Pharmaceuticals, Inc.