Design of GFB-111, a platelet-derived growth factor binding molecule with antiangiogenic and anticancer activity against human tumors in mice.
| Abstract |
We have designed a molecule, GFB-111, that binds to platelet-derived growth factor (PDGF), prevents it from binding to its receptor tyrosine kinase, and blocks PDGF-induced receptor autophosphorylation, activation of Erk1 and Erk2 kinases, and DNA synthesis. GFB-111 is highly potent (IC50 = 250 nM) and selective for PDGF over EGF, IGF-1, aFGF, bFGF, and HRGbeta (IC50 values > 100 microM), but inhibits VEGF-induced Flk-1 tyrosine phosphorylation and Erk1/Erk2 activation with an IC50 of 10 microM. GFB-111 treatment of nude mice bearing human tumors resulted in significant inhibition of tumor growth and angiogenesis. The results demonstrate the feasibility of designing novel growth factor-binding molecules with potent anticancer and antiangiogenic activity. |
| Authors | M A Blaskovich, Q Lin, F L Delarue, J Sun, H S Park, D Coppola, A D Hamilton, S M Sebti |
| Journal | Nature biotechnology
(Nat Biotechnol)
Vol. 18
Issue 10
Pg. 1065-70
(Oct 2000)
ISSN: 1087-0156 [Print] United States |
| PMID | 11017044
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Angiogenesis Inhibitors
- Antineoplastic Agents
- Endothelial Growth Factors
- GFB 111
- Lymphokines
- Peptides, Cyclic
- Platelet-Derived Growth Factor
- Receptors, Growth Factor
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- DNA
- Receptor Protein-Tyrosine Kinases
- Receptors, Platelet-Derived Growth Factor
- Receptors, Vascular Endothelial Growth Factor
- Mitogen-Activated Protein Kinases
|
| Topics |
- Angiogenesis Inhibitors
(chemistry, metabolism, pharmacology, therapeutic use)
- Animals
- Antineoplastic Agents
(chemistry, metabolism, pharmacology, therapeutic use)
- Cell Division
(drug effects)
- Cell Line
- DNA
(biosynthesis)
- Drug Design
- Endothelial Growth Factors
(antagonists & inhibitors, pharmacology)
- Enzyme Activation
(drug effects)
- Glioblastoma
(blood supply, drug therapy, pathology)
- Humans
- Inhibitory Concentration 50
- Lymphokines
(antagonists & inhibitors, pharmacology)
- Mice
- Mice, Nude
- Mitogen-Activated Protein Kinases
(metabolism)
- Neoplasm Transplantation
- Neovascularization, Pathologic
(drug therapy)
- Peptides, Cyclic
(chemistry, metabolism, pharmacology, therapeutic use)
- Phosphorylation
(drug effects)
- Platelet-Derived Growth Factor
(antagonists & inhibitors, metabolism, pharmacology)
- Receptor Protein-Tyrosine Kinases
(metabolism)
- Receptors, Growth Factor
(metabolism)
- Receptors, Platelet-Derived Growth Factor
(antagonists & inhibitors, metabolism)
- Receptors, Vascular Endothelial Growth Factor
- Substrate Specificity
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|
