Table 27.1.
Mitochondria-targeted therapeutics
| Therapeutics | Chemicals | Action mechanisms | Experimental model |
|---|---|---|---|
| Antioxidants | |||
| MitoQa | Mitoquinone | Anti-oxidant concentrate at matrix in a ΔΨm-dependent manner; ROS scavenger | IRI-AKI, cisplatin-AKI, sepsis-AKI |
| Biogenesis activator | |||
| Resveratrol (SRT501) | Small peptides | AMPK / SIRT-1 / PGC-1α axis activator | Hemorrhagic shock, sepsis-AKI |
| AICAR | SIRT3 activator, AMPK agonist | Cisplatin-AKI, IRI-AKI | |
| Formoterol | β2-adrenoceptor agonist, increase PGC-1α synthesis | IRI-AKI | |
| ROS metabolism and bioenergetics | |||
| Mitochonic acid (MA-5) | Synthetic compound | OXPHOS-independent increase of ATP synthesis, reduce ROS | Sepsis-AKI |
| Cardiolipin protection | |||
| Bendavia (SS-31)a | Szeto-Schiller tetrapeptide | Protect cardiolipin from peroxidation; increase ATP and reduce ROS | AKI and CKD |
| Prevent cyt C transformation into peroxidase | |||
| mPTP inhibitor | |||
| cyclosporin A (CsA)a | Small molecule | Interact with cyclophilin D (a mPTP structural protein) | Adriamycin-induced podocyte injury |
| TDZD-8 | mPTP inhibitors, GSK3β inhibitor | Podocyte injury or drug induced AKI | |
| Fission inhibitor | |||
| Mdivil | Small molecule | Inhibitor of mitochondrial division; induce mitochondria fusion | IRI-AKI |
| Block DRP1 assembly and translocation | |||
| K(ATP) channel opener | |||
| Simdax (Levosimendan)a | Small molecule | Calcium sensitizer, K(ATP) channel opener | IRI-AKI |
| cyt C assembly | |||
| KLF6 | DNA-binding zinc finger transcriptional regulator | enhance cyt C assembly | Podocytes FSGS (animal study) |
a
Clinical trials. https://clinicaltrials.gov