Drugs acting on mitochondrial permeability transition
| Reagent | Principle | Reference | Experimental Effects | Clinical Trial/Status |
|---|---|---|---|---|
| Peripheral benzodiazepine receptor ligands | PK11195, Ro5—4864, FGIN-1—27 | Hirsch et al., 1998; Maaser et al., 2001 | Potentiate chemosensitivity, induce tumor xenograft regression | Preclinical |
| Lonidamine | Dichlorinated indazole-3-carboxylic acid derivative | Ravagnan et al., 1999 | Permeabilizes isolated mitochondria, potentiates chemotherapeutic effects | Phase 2/3 in metastatic breast cancer and non-small cell lung carcinoma |
| CD437 | Synthetic retinoid | Marchetti et al., 1999 | Apoptosis induction in several tumor cells, MMP transition in vitro (several other actions known) | Preclinical |
| Cladribine | 2-Chloro-2′-deoxyadenosine | Genini et al., 2000 | Direct disruption of mitochondrial membrane potential | Approved for chronic lymphocytic and hairy cell leukemia |
| Arsenite | Arsenic trioxide | Larochette et al., 1999 | Oxidative disruption of mitochondrial membrane and proteins | Approved for acute promyelocytic leukemia |
| D(KLAKLAK2)2 | Positively charged α-helical peptide | Ellerby et al., 1999 | Disrupts mitochondrial membranes and shows anticancer activity in mice | Preclinical |
| Verteporfin | Porphyrine photosensitizer | Belzacq et al., 2001 | Direct triggering of cytochrome c release | Used in photodynamic therapy |
| Betulinic acid | Pentacyclic triterpenoid from Birch | Pisha et al., 1995; Fulda et al., 1998 | Proapoptotic activity in isolated mitochondrial cell lines and xenograft models | Preclinical |
| MKT-077 | Cationic rhodacyanine | Modica-Napolitano et al., 1996 | Selective cytotoxicity for tumor cells, also mitochondria-independent actions known | Phase 1 |