Table VI.
Migration inhibitors in clinical development
| Drug | Target | Company | Clinical Phase | Reference |
|---|---|---|---|---|
|
| ||||
| Cell autonomous | ||||
|
| ||||
| Saracatinib (AZD0530) | Src | AstraZeneca | II | [126] |
| Bosutinib (SKI-606) | Src | Wyeth | II, III | [127] |
| Dasatinib (BMS-354825) | Src | Bristol-Myers Squibb | I, II | [128] |
| Fasudil | Rho kinase | Asahi Kasei | I, II, III | [129] |
| Emodin | Cdc42/Rac1 | I | [130] | |
|
| ||||
| Soluble interactions | ||||
|
| ||||
| CTCE-9908 | SDF-1 | Chemokine Therapeutics | I, II | [131] |
| MetMAB (PRO143966) | Met | Roche/Genentech | II | [132] |
| AMG 208 | Met | Amgen | I | Clinical Trial NCT00813384 |
| GC1008 | TGF-β family | Genzyme | I, II | J Clin Oncol 26:2008 (ASCO Abstr. 9028) |
| Trabedersen (AP 12009) | TGF-β2 | Antisense Pharma | I, II | [133] |
| Infliximab | TNF-α | Centocor | I, II | [134] |
| EGFR | Herceptin^ (trastuzumab) | Genentech/Roche | I, II, III | Trial NCT00807859 |
| VEGF | Avastin^ | Genentech/Roche | I, II, III | Clinical Trial NCT00391092 Clinical Trial NCT00333775 |
| CXCR-4 | CTCE-9908 | Chemokine Therapeutics | I, II | [146, 147] |
|
| ||||
| Cell-cell interactions | ||||
|
| ||||
| IGN-101 | EpCAM | Aphton | I, II | J Clin Oncol 26: 2008 (ASCO Abstr. 15) |
| Exherin (ADH-1) | N-cadherin | Adherex | I, II | [135] |
|
| ||||
| Cell-matrix interactions | ||||
|
| ||||
| Cilengitide (EMD121974) | αvβ and αvβ5 integrins | EMD/Merck KGaA | II, III | [136] |
| Volociximab (M200) | α5β1 integrin | PDL/Biogen Idec | II | [137] |
| Etaracizumab (Abegrin) | αvβ3 integrin | MedImmune | I, II | [138] |
| ATN-161 | Integrins | Tactic Pharmaceuticals | I, II | [139] |
| BMS-275291# | MMPs | Bristol-Myers Squibb | I, II, III | [140] |
| Endostatin | MMPs | Alchemgen Therapeutics | III | [141] |
| Curcumin | MMPs | Sabinsa Corporation | I, II | [125] |
| Tigapotide (PCK3145) | MMP9 | Ambrilia Biopharma | II | [142] |
| A6 | CD44 | Angstrom Pharmaceuticals | II | Clinical Trial NCT00083928 |
| Mesupron (WX-671) | uPA | Wilex | I, II | [143] |
| ATN-658 | uPA | Tactic Pharmaceuticals | I | http://www.tacticpharma.com/ATN-658.html |
| Tempostatin (Halofuginone hydrobromide) | Stroma | Collgard Pharmaceuticals | II | [144] |
| PI-88 | Heparanase | Progen | I, II, III | [145] |
| Vitaxin | αvβ3 | MedImmune | II | Trial NCT00072930 |
|
| ||||
| Molecular integration | ||||
|
| ||||
| CFAK-C4 | FAK | CureFAKtor Pharmaceuticals | I | www.curefaktor.com |
| PF-562271 | FAK | Pfizer | I | J Clin Oncol 28: 2010 (ASCO abstr. 2553) |
^
Small molecule inhibitors capable of blocking EGFR and VEGFR kinase activity (compound A and B respectively) have also been developed and are currently being evaluated in advanced and metastatic disease. Resistance to both Herceptin and Avastin occurs frequently.
#
Broad MMP inhibitors failed in the clinic due to their negative impact on normal tissue remodeling. Enzyme-specific MMP inhibitors are currently pursued for a more directed approach. For instance ADAM17 inhibitors may inhibit TNFα activation and shedding of IgSF members.