TABLE 3 | Clinical trials of drugs that have shown anti-angiogenic activity in preclinical models
From the following article:
Angiogenesis: an organizing principle for drug discovery?
Judah Folkman
Nature Reviews Drug Discovery 6, 273-286 (April 2007)
doi:10.1038/nrd2115
| Inhibitor (Company) | Target/mechanism | Clinical development |
|---|---|---|
| 2-methoxyestradiol-EntreMed (EntreMed) | Inhibits HIF1 and tubulin polymerization |  Phase I: Breast cancer and solid tumours Phase II: Glioblastoma, multiple myeloma, neuroendocrine, renal cell, prostate, ovarian cancer |
| A6 (Angstrom Pharmaceuticals) | Binds to uPA cell-surface receptor | Phase II: History of ovarian cancer with rising CA125 |
| Abergrin (MedImmune) | Antiv 3 antibody | Phase I: Melanoma, solid tumours, colorectal cancer Phase II: Melanoma, prostate cancer, psoriasis, arthritis |
| ABT-510 (Abbott Laboratories) | Thrombospondin 1 receptor CD36 | Phase I: Head and neck cancer, solid tumours Phase II: Lymphoma, renal cell, head and neck, NSCLC, soft tissue sarcoma |
| Actimid (Celgene Corporation) | Downregulates TNF | Phase II: Prostate cancer (completed) |
| AG-013736 (Pfizer) | VEGFR, PDGFR | Phase I: Breast cancer Phase II: NSCLC, melanoma, thyroid, breast, pancreatic, renal cell cancer |
| AMG706 (Amgen) | VEGFR, PDGFR, KITR, RETR | Phase I: Lymphoma, solid tumours, NSCLC, breast, colorectal cancer Phase II: Solid tumours, NSCLC, gastrointestinal stromal tumours (GIST), breast, thyroid cancer |
| AP23573 (Ariad Pharmaceuticals) | mTOR, VEGF | Phase I: Glioma, sarcoma, solid tumours, multiple myeloma Phase II: Endometrial cancer, prostate cancer, haem malignancies |
| AS1404 (Antisoma) | Vascular disrupting agent, releases TNF and vWF | Phase II: Prostate cancer |
| ATN-161 (Attenuon) | 51 antagonist | Phase II: Renal cell cancer, malignant glioma |
| AZD2171 (AstraZeneca) | VEGFR1, VEGFR2, VEGFR3, PDGFR | Phase I: NSCLC, AML, colorectal, head and neck cancer, CNS tumours (child) Phase II: Solid tumours, NSCLC, glioblastoma, melanoma, mesothelioma, neurofibromatosis, ovarian, CLL, colorectal, breast, kidney, liver, SCLC Phase III: NSCLC |
| BMS-275291 (Bristol–Myers Squibb) | MMP inhibitor | Phase I: Kaposi's sarcoma Phase II: Kaposi's sarcoma, prostate cancer, NSCLC Phase III: NSCLC |
| CCI-779 (Wyeth) | mTOR, VEGFR | Phase I: Solid tumours, prostate cancer, CML, and others Phase II: CLL, melanoma, glioblastoma, multiple myeloma, GIST, SCLC, NHL, NSCLC, neuroendocrine tumours, breast, pancreatic, endometrial cancer, and others |
| CDP-791 (Imclone Systems) | VEGFR2, KDR | Phase II: NSCLC |
| Celecoxib (Pfizer) | Increases endostatin | Phase I: NSCLC, pancreatic, prostate cancer, solid tumours Phase II: Head and neck cancer prevention, breast cancer prevention, lung cancer prevention, NSCLC, paediatric solid tumours, Ewing's sarcoma, glioma, skin cancer prevention, basal cell nevus syndrome, Barrett's oesophagus, hepatocellular, oesophogael, prostate, cervical, colorectal, head and neck, breast, thyroid, nasopharyngeal cancer, and others Phase III: Colon, prostate, bladder cancer, NSCLC, and others |
| Cilengitide (EMD Pharmaceuticals) | v3 and 5 antagonist | Phase I: Solid tumours, lymphomas, paediatric brain tumours Phase II: Glioblastoma, gliomas |
| Combretastatin (Oxigene) | VE-cadherin | Phase I: Solid tumours Phase II: Solid tumours, anaplastic thyroid cancer |
| E7820 (Eisia Medical Research Inc.) | Inhibits integrin 2 subunit on endothelium | Phase I: Lymphoma Phase II: Colorectal cancer |
| Everolimus (Novartis) | VEGFR, mTOR | Phase I: Breast cancer, solid tumours, lymphoma Phase II: NSCLC, melanoma, AML, ALL, CML, lymphoma, glioblastoma, prostate, colorectal, neuroendocrine, breast, endometrial, kidney cancer, paediatric tumours, solid tumours Phase III: Islet cell pancreas II/III, and others |
| Genistein (National Cancer Institute (NCI), USA) | Suppresses VEGF and neuropilin and MMP9 in tumour cells, upregulates CTAP | Phase I: Melanoma, kidney, prostate, bladder, breast cancer |
| Homoharringtonine (ChenGenex Therapeutics) | Downregulates VEGF in leukaemic cells | Phase II: CML, APML Phase III: CML |
| IMC-1121b (Imclone Systems) | VEGFR2, KDR | Phase I: Solid tumours |
| INGN 241 (Introgen Therapeutics) | MDA7, VEGF | Phase II: Melanoma |
| Interleukin-12 (NCI) | Upregulates IP10 | Phase I: Solid tumours, melanoma, paediatric neuroblastoma, kidney, breast cancer Phase II: Melanoma, NHL, multiple myeloma, breast, ovarian, peritoneal, prostate cancer |
| Enzastaurin (Eli Lilly and Company) | VEGF | Phase I: Solid tumours, gliomas Phase II: Gliomas, lymphoma, brain tumours, NSCLC, pancreatic, colorectal cancer Phase III: Lymphoma prevention, glioblastoma |
| Neovastat (Aeterna Zentaris) | MMP inhibitor | Phase II: Multiple myeloma Phase III: Kidney, NSCLC |
| NM-3 (Genzyme Corporation) | Inhibits VEGF expression by tumour cells, inhibits endothelial proliferation | Phase I: Solid tumours |
| NPI-2358 (Nereus Pharmaceuticals) | -tubulin | Phase I: Solid tumours |
| Phosphomannopentaose sulphate (Progen Industries, Medigen Biotechnology) | bFGF, stimulates release of TFP1 | Phase II: Melanoma, NSCLC, prostate, hepatocellular cancer |
| PKC412 (Novartis) | VEGFR2 | Phase I: AML Phase II: Mast-cell leukaemia |
| PPI-2458 (Praecis) | METAP2 | Phase I: Solid tumours, NHL |
| Prinomastat (Agouron Pharmaceuticals) | MMP inhibitor | Phase II: Glioblastoma |
| PXD101 (CuraGen Corporation) | HDAC inhibitor | Phase I: Solid tumours, haem malignancies Phase II: Multiple myeloma, myelodysplastic syndrome, lymphoma, AML, NHL, ovarian/peritoneal, liver cancer |
| Suramin (NCI) | IGF1, EGFR, PDGFR, TGF, inhibits VEGF and bFGF | Phase I: Bladder, breast, kidney cancer Phase II: Glioblastoma, breast, kidney, adrenocortical cancer Phase III: Prostate cancer |
| Tempostatin (Collard Biopharmaceuticals) | Extracellular matrix proteins | Phase I: Solid tumours Phase II: Kaposi's sarcoma |
| Tetrathiomolybdate (Sigma-Aldrich) | Copper chelator | Phase II: Prostate, oesophageal, breast, colorectal cancer Phase III: Psoriasis |
| TKI-258 (Novartis, Chiron Corporation) | FGFR3, VEGFR | Phase I: Multiple myeloma, AML, melanoma |
| Vatalanib (Novartis) | VEGFR1,2, PDGFR | Phase I: Solid tumours, NSCLC, gynaelogic tumours Phase II: GIST, AML, CML, solid tumours, NSCLC, VHL, haemangioblastoma, mesothelioma, breast, prostate, pancreatic, neuroendocrine cancer, glioblastoma, meningioma, myelodysplastic syndrome, multiple myeloma, age-related macular degeneration Phase III: Colorectal cancer |
| VEGF Trap (Regeneron Pharmaceuticals) | VEGF | Phase I: NHL, age-related macular degeneration, diabetic macular oedema Phase II: Kidney, ovarian cancer, NSCLC, age-related macular degeneration Phase III: Ovarian cancer |
| XL184 (Exelixis) | MMET, VEGFR, RTK, FLT3, TIE2 | Phase I: Solid tumours |
| XL880 (Exelixis) | C-met, RTK | Phase I: Solid tumours Phase II: Papillary renal cell carcinoma |
| XL999 (Exelixis) | VEGFR, PDGFR, EGFR, FLT3, Src | Phase I: Solid tumours Phase II: Multiple myeloma, colorectal, ovarian, renal cell cancer, AML, NSCLC |
| ZD6474 (AstraZeneca) | VEGFR2, EGFR | Phase I: Glioma Phase II: Breast cancer, NSCLC, SCLC, thyroid, gliomas, multiple myeloma Phase III: NSCLC |
| AML, acute myeloid leukaemia; APML, acute promyelocytic leukaemia; bFGF, basic fibroblast growth factor; CML, chronic myeloid leukaemia; CLL, chronic lymphocytic leukaemia; CNS, central nervous system; CTAP, connective tissue activation peptide; EGFR, epidermal growth factor receptor; FGFR3, fibroblast growth factor receptor 3; FLT3, fms-related tyrosine kinase 3; HDAC, histone deacetylase; HIF1, hypoxia-inducible factor 1; IGF1, insulin-like growth factor 1; IP10, inducible protein 10; KDR, kinase insert domain receptor; MDA7, interleukin-24; METAP2, methionyl aminopeptidase 2; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; NHL, non-Hodgkin's lymphoma; NSCLC, non-small-cell lung cancer; PDGFR, platelet-derived growth factor receptor; RETR, ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease) receptor; SCLC, small-cell lung cancer; TFP1, transferrin pseudogene 1; TGF, transforming growth factor-; TNF, tumour-necrosis factor; uPA, urokinase-type plasminogen activator; VE-cadherin, vascular/endothelial-cadherin; VEGF(R), vascular endothelial growth factor (receptor); vWF, von Willebrand factor. | ||
Download file
If the slide opens in your browser, select "File > Save As" to save it.
