Table 1.
Summary of the developmental status of anti-cancer agents targeting mitochondrial apoptotic machinery.
| Agent | Target or mode of action | Phase of clinical development | References |
|---|---|---|---|
| MODULATORS OF THE Bcl-2 FAMILY PROTEINS | |||
| ABT-263 | Bcl-2, Bcl-XL, Bcl-W | Phase II | Rudin et al., 2012 |
| ABT-737 | Bcl-2, Bcl-XL, Bcl-W | Pre-clinical (in vitro and in vivo) | Mason et al., 2008 |
| AT-101 (gossypol) | Bcl-2, Bcl-XL, Bcl-W, Mcl-1 | Phase II | Van Poznak et al., 2001 |
| GX15-070 (obatoclax) | Bcl-2, Bcl-XL, Bcl-W, Mcl-1 | Phase II | Parikh et al., 2010 |
| HA14-1 | Bcl-2 | Pre-clinical (in vitro and in vivo) | Simonin et al., 2009 |
| G3139 (oblimersen) | Bcl-2 mRNA antisense | Phase III | O'Brien et al., 2007 |
| METABOLIC INHIBITORS | |||
| Methyl jasmonate | HK II-VDAC interaction | Pre-clinical (in vitro and in vivo) | Goldin et al., 2008 |
| 3-Bromopyruvate | HK II-VDAC interaction | Pre-clinical (in vitro and in vivo) | Chen et al., 2009 |
| HK II peptide | HK II-VDAC interaction | Pre-clinical (in vitro) | Chiara et al., 2008 |
| VDAC AND/OR ANT-TARGETING AGENTS | |||
| Arsenite trioxide (As2O3) | ANT ligand, ROS production | Phase IV | Powell et al., 2010 |
| Lonidamine | ANT ligand | Phase IV | Di Cosimo et al., 2003; Oudard et al., 2003 |
| Clodronate | ANT inhibitor | Phase III | Lehenkari et al., 2002 |
| GSAO | ANT cross linker | Pre-clinical (in vitro and in vivo) | Don et al., 2003 |
| FNQs | VDAC1 | Pre-clinical (in vitro and in vivo) | Simamura et al., 2006 |
| Erastin | VDAC2 and VDAC3 | Phase I | NCT00528047 |
| ROS REGULATORS | |||
| Motexafin gadolinium | ROS production, Akt | Phase III | Mehta et al., 2009 |
| Bismaleimido-hexane | ANT thiol oxidation | Pre-clinical (in vitro) | Palmeira and Wallace, 1997 |
| Dithiodipyridine | ANT thiol oxidation | Pre-clinical (in vitro and in vivo) | Lifson et al., 2004 |
| RETINOIDS | |||
| All-trans-retinoid acid | ANT ligand | Pre-clinical (in vitro and in vivo) | Notario et al., 2003 |
| CD437 | MPTP | Pre-clinical (in vitro) | Marchetti et al., 1999; Belzacq et al., 2001 |
| NATURAL COMPOUNDS | |||
| Resveratrol | F1-ATPase | Phase II | Gledhill et al., 2007 |
| Curcumin | Bax, Bcl-2, Bcl-XL, NF-κ B | Phase III | Carroll et al., 2011 |
| Betulinic acid | MPTP | Pre-clinical (in vitro) | Fulda et al., 1997 |
| Berberine | ANT ligand | Pre-clinical (in vitro and in vivo) | Pereira et al., 2008 |
| α-tocopheryl succinate | Bax, ubiquinone-binding sites in respiratory complex II | Pre-clinical (in vitro and in vivo) | Dong et al., 2008 |
| Honokiol | Cyclophilin D | Pre-clinical (in vitro and in vivo) | Arora et al., 2012 |
ANT, adenine nucleotide translocase; GSAO, 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide; CD437, 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid; HA14-1, 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; HK, hexokinase; Mcl-1, myeloid cell leukemia sequence 1; MPTP, mitochondrial permeability transition pore; ROS, reactive oxygen species; VDAC, voltage-dependent anion channel. Modified and adapted by permission from Fulda et al. (2010) and Barbosa et al. (2012).