Anti-angiogenic agents in clinical trials.
| Target . | Agent (Source) . | Description . | Action . | Ref. . |
|---|---|---|---|---|
| Abbreviations: MoAb, monoclonal antibody; VEGF, vascular endothelial growth factor; EC, endothelial cell; ECM, extracellular matrix; MMP, matrix metalloprotease; TKI, tyrosine kinase inhibitor; IFN, interferon; FTI, farnesyl transferase inhibitor; i.v., intravenous; po, per oral; IL, interleukin; FGF, fibroblast growth factor; bFGF, basic FGF; TNFα, tumor necrosis factor-α | ||||
| Angiogenic Factors | Bevacizumab (Genentech) | humanized MoAb | VEGF neutralization | 110,111 |
| IM862 (Cytran) | small peptide | ↓VEGF + bFGF production, ‐IL-12 | 112 | |
| IFNα (Schering, Roche) | recombinant protein | ↓VEGF + bFGF production, | 113 | |
| ↓EC proliferation | ||||
| Angiongenic Receptors | 2C3 | murine MoAb | VEGFR-2 antagonist | 114 |
| CD101 (ImClone) | rat MoAb | VEGFR-2 antagonist | 115 | |
| Angiozyme (Ribozyme) | VEGFR catalytic ribozyme | VEGFR-1,2 mRNA inactivation | 116 | |
| SU5416 (Sugen) | small molecule, i.v. | VEGFR1,2-TKI, c-kit, PDGFR | 92,117 | |
| SU11248 (Sugen) | small molecule, po | VEGFR1,2-TKI, c-kit, PDGFR, FGF | ||
| PTK787/ZK222584 (Novartis) | small molecule, po | VEGFR1,2-TKI, c-kit, PDGFR, FGF, c-fms | 118 | |
| AG13736 (Agouron) | small molecule, po | VEGFR1,2-TKI, c-kit, PDGFR, FGF | ||
| Vascular Adhesion Molecules | SCH221153 (Schering) | peptidomimetic | αvβ3 + αvβ5 antagonist, EC apoptosis | 119 |
| Vitaxin (Ixsys) | humanized MoAb | αvβ3antagonist, EC apoptosis | 120 | |
| Activated Endothelial Cells | Endostatin (EntreMed) | collagen XVIII fragment | ↓EC proliferation, EC apoptosis | 121,122 |
| Vasostatin | calreticulin fragment | ↓EC proliferation | 123 | |
| TNP-470 (TAP Pharma.) | fumagillin analogue | ↓EC proliferation | 124 | |
| 2-methoxyestradiol | estrogen metabolite | EC apoptosis | 125 | |
| Thalidomide (Celgene) | phthalimidoglutarimide | ↓EC proliferation (bFGF,VEGF) ↓TNFα | 85 | |
| CC-5013 (Celgene) | phtaloyl analogue | ↓EC proliferation, ↓TNFα, Th1 stimulator | 86 | |
| Arsenic trioxide (CTI) | trivalent arsenical | EC apoptosis, tumor cytotoxin | 126 | |
| SCH66336 (Schering) | non-peptide, FTI | ↓EC proliferation, ↓VEGF | 127,128 | |
| R115777 (Janssen) | non-peptide, FTO | ↓EC proliferation, ↓VEGF | 91 | |
| ECM Remodelling | Prinomastat (Agouron) | non-peptide hydroxymate | MMP inhibition | 81 |
| Target . | Agent (Source) . | Description . | Action . | Ref. . |
|---|---|---|---|---|
| Abbreviations: MoAb, monoclonal antibody; VEGF, vascular endothelial growth factor; EC, endothelial cell; ECM, extracellular matrix; MMP, matrix metalloprotease; TKI, tyrosine kinase inhibitor; IFN, interferon; FTI, farnesyl transferase inhibitor; i.v., intravenous; po, per oral; IL, interleukin; FGF, fibroblast growth factor; bFGF, basic FGF; TNFα, tumor necrosis factor-α | ||||
| Angiogenic Factors | Bevacizumab (Genentech) | humanized MoAb | VEGF neutralization | 110,111 |
| IM862 (Cytran) | small peptide | ↓VEGF + bFGF production, ‐IL-12 | 112 | |
| IFNα (Schering, Roche) | recombinant protein | ↓VEGF + bFGF production, | 113 | |
| ↓EC proliferation | ||||
| Angiongenic Receptors | 2C3 | murine MoAb | VEGFR-2 antagonist | 114 |
| CD101 (ImClone) | rat MoAb | VEGFR-2 antagonist | 115 | |
| Angiozyme (Ribozyme) | VEGFR catalytic ribozyme | VEGFR-1,2 mRNA inactivation | 116 | |
| SU5416 (Sugen) | small molecule, i.v. | VEGFR1,2-TKI, c-kit, PDGFR | 92,117 | |
| SU11248 (Sugen) | small molecule, po | VEGFR1,2-TKI, c-kit, PDGFR, FGF | ||
| PTK787/ZK222584 (Novartis) | small molecule, po | VEGFR1,2-TKI, c-kit, PDGFR, FGF, c-fms | 118 | |
| AG13736 (Agouron) | small molecule, po | VEGFR1,2-TKI, c-kit, PDGFR, FGF | ||
| Vascular Adhesion Molecules | SCH221153 (Schering) | peptidomimetic | αvβ3 + αvβ5 antagonist, EC apoptosis | 119 |
| Vitaxin (Ixsys) | humanized MoAb | αvβ3antagonist, EC apoptosis | 120 | |
| Activated Endothelial Cells | Endostatin (EntreMed) | collagen XVIII fragment | ↓EC proliferation, EC apoptosis | 121,122 |
| Vasostatin | calreticulin fragment | ↓EC proliferation | 123 | |
| TNP-470 (TAP Pharma.) | fumagillin analogue | ↓EC proliferation | 124 | |
| 2-methoxyestradiol | estrogen metabolite | EC apoptosis | 125 | |
| Thalidomide (Celgene) | phthalimidoglutarimide | ↓EC proliferation (bFGF,VEGF) ↓TNFα | 85 | |
| CC-5013 (Celgene) | phtaloyl analogue | ↓EC proliferation, ↓TNFα, Th1 stimulator | 86 | |
| Arsenic trioxide (CTI) | trivalent arsenical | EC apoptosis, tumor cytotoxin | 126 | |
| SCH66336 (Schering) | non-peptide, FTI | ↓EC proliferation, ↓VEGF | 127,128 | |
| R115777 (Janssen) | non-peptide, FTO | ↓EC proliferation, ↓VEGF | 91 | |
| ECM Remodelling | Prinomastat (Agouron) | non-peptide hydroxymate | MMP inhibition | 81 |