A New Series of Thalidomide Analogs with Potent Anti-Angiogenic and Anti-Cancer Properties
Background:
The Medical Oncology Branch of
the National Cancer Institute seeks a Cooperative Research and
Development Agreement (CRADA) collaborator for preclinical and
clinical development of thalidomide analogs.
The classical orally active drug, thalidomide
(N-alpha-phthalimidoglutarimide), a glutamic acid derivative, is
being increasingly used in the clinical management of a wide
spectrum of immunologically-mediated and infectious diseases, and
cancers. Thalidomide's anti-cancer activity has been shown to occur
via a wide range of mechanisms, and numerous analogs have been
designed, primarily targeting immunomodulatory pathways, including
inhibition of TNF-alpha expression.
Technology:
Several fluorinated thalidomide
analogs have been shown to possess excellent anti-angiogenic and
anti-tumor activity, both in vitro and in vivo. Two series of
second generation tetrafluorinated compounds have now been
synthesized and tested. The first series is based on a modified
thalidomide structure, while the second series is comprised of
tetrafluorobenamides, without the intact pthalimido-group. Analogs
from both series have shown significant ex vivo and in vitro
anti-angiogenic activity, along with in vitro anti-cancer activity.
This activity is superior to that found with first generation
tetrafluorinated thalidomide analogs.
IP
Status:
U.S. Provisional Application and PCT
Applications filed.
Value Proposition:
- Two series of tetrahalogenated thalidomide derivatives, based
on two major common pharmacophores that are potentially more
anti-angiogenic than thalidomide.
- Analogs from both series have shown significant ex vivo and in
vitro anti-angiogenic and anti-cancer activity.
- Methods for using these compounds to treat solid tumors.
Follow-on
Research/Development:
- Preclinical development including identification of lead
compound(s) by:
-
- Preclinical toxicity studies, along with mouse xenograft
studies to assess activity
- Preclinical pharmacokinetics, including drug formulation
studies
- Teratogenicity testing
- Subsequent clinical development of selected lead(s)
Contact
Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #523 MP
Updated on 10/17/2007