North American researchers have chemically
synthesized a d-protein ligand
that blocked the binding of VEGF
to its receptor in vitro.1
Reflexion Pharmaceuticals Inc. has licensed the compound and thinks it could have better
stability and bioavailability than anti-VEGF antibodies that are l-isomer proteins. The company is
optimizing its molecule before doing head-to-head comparisons with Lucentis
in animal models of age-related macular degeneration.
The right-hand path
Reflexion "has already produced
affinity-matured, next-generation molecules based on the initial lead in the PNAS
article," Sidhu told SciBX. He added that the best antagonists "will be
validated in cell-based assays to assess inhibition of VEGF activity in
physiologically relevant systems and also tested in animal models of
age-related macular degeneration and cancer, in comparison with Lucentis and
Fulmer, T. SciBX 5(36);
Published online Sept. 13, 2012
1. Mandal, K. et al. Proc. Natl.
Acad. Sci. USA; published online
Aug. 27, 2012; doi:10.1073/pnas.1210483109
Contact: Sachdev S. Sidhu, University of Toronto, Toronto, Ontario,
Contact: Stephen B.H. Kent, The University of Chicago, Chicago,
2. Sun, N. et al. J.
Biotechnol. 161, 121-125 (2012)
3. Mandal, K. & Kent,
Chem. Int. Ed. 50, 8029-8033 (2011)
4. Schumacher, T.N.M. et al. Science 271, 1854-1857
5. Funke, S.A. &
Willbold, D. Mol. Biosyst. 5, 783-786 (2009)
6. Zhan, C. et al. J. Med. Chem. 55, 6237-6241
7. Welch, B.D. et al. J. Virol. 84, 11235-11244
8. Welch, B.D. et al. Proc. Natl.
Acad. Sci. USA 104, 16828-16833 (2007)
9. Aileen Funke, S. et al. ACS Chem.
Neurosci. 1, 639-648 (2010)
Chugai Pharmaceutical Co. Ltd. (Tokyo:4519), Tokyo, Japan
Genentech Inc., South San Francisco, Calif.
Heinrich Heine University of Duesseldorf, Duesseldorf, Germany
Massachusetts Institute of Technology, Cambridge, Mass.
Merck & Co. Inc. (NYSE:MRK), Whitehouse Station, N.J.
Navigen Pharmaceuticals Inc., Salt Lake City, Utah
Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland
Ontario Institute for Cancer Research, Toronto, Ontario, Canada
Reflexion Pharmaceuticals Inc., San Francisco, Calif.
(SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
Stanford University School of Medicine, Palo Alto, Calif.
The University of Chicago, Chicago, Ill.
University of Maryland School of Medicine, Baltimore, Md.
University of Toronto, Toronto, Ontario, Canada
The University of Utah School of Medicine, Salt Lake City, Utah
Whitehead Institute for Biomedical Research, Cambridge, Mass.