Table 1.
Mitochondria-targeting drugs that are used in kidney diseases.
| Drug Name | MECHANISM of Action | Animal Models | Clinical Trials on Kidney Disease Identifier Number |
Kidney Diseases Studied on Humans |
|---|---|---|---|---|
| Cardiolipin Protective Agents | ||||
| SS-31 | Binds cardiolipins, prevents their peroxidation, and maintains mitochondrial membrane structure, ROS scavenger | Unilateral ureteral obstruction (98, 99), sepsis-induced acute kidney injury (100), diabetic kidney disease (102–105), renovascular disease (106), metabolic syndrome (107–109), ischemia-reperfusion acute kidney injury (110, 111), contrast-induced nephropathy (113), cisplatin-induced acute kidney injury (114), chronic kidney disease (13, 87, 112) | NCT01755858, NCT02436447 | NCT02436447: patients with renal impairment NCT01755858: percutaneous transluminal renal angioplasty |
| SS-20 | Binds cardiolipin and maintains mitochondrial membrane structure, but does not scavenger ROS and inhibit inner mitochondrial membrane transition | Warm ischemia kidney models and ischemia-induced fibrosis (117) | N/A | N/A |
| Fission inhibitors | ||||
| mdivi-1 | Selectively inhibits DRP1 GTPase and favors mitochondrial fusion | Septic acute kidney injury (124, 125), cisplatin-induced acute kidney injury (11), ischemia reperfusion-induced acute kidney injury (11, 126), autosomal dominant polycystic kidney disease (55), chronic kidney disease (123), diabetic kidney disease (127), unilateral renal obstruction (78, 123) | N/A | N/A |
| mPTP Inhibitors | ||||
| TDZD-8 | Inhibits glycogen synthase kinase 3b and prevents mPTP channel opening | Adriamycin-induced kidney damage (140), ischemia-reperfusion acute kidney injury (141), NSAID-induced acute kidney injury (142) | N/A | N/A |
| Alisporivir | Analogue of cyclosporine A. Binds cyclophilin and inhibits mPTP channels | Diabetic kidney disease (143) | NCT01975337 | NCT01975337: hemodialysis patients |
| Biogenesis Activators | ||||
| SRT1720 | Activates Sirtuin1 and mitochondrial biogenesis | Unilateral ureteral obstruction (144), chronic kidney disease (144, 145), cisplatin-induced acute kidney injury (146), ischemia-reperfusion acute kidney injury (147, 148) | N/A | N/A |
| LY344864 | Selectively activates 5-HT1F receptor and activates mitochondrial biogenesis | Ischemia-reperfusion acute kidney injury (150) | N/A | N/A |
| BF175 | Selectively activates Sirtuin1 and mitochondrial biogenesis | Diabetic kidney disease (151), HIV kidney disease (152) | N/A | N/A |
| Resveratrol | Activates mitochondrial biogenesis and ROS scavenger | Diabetic kidney disease (153, 154), ischemia-reperfusion acute kidney injury (155) | NCT02433925, NCT03352895, NCT03597568, NCT03815786, NCT02704494, NCT03946176 | NCT02433925, NCT03352895, NCT03597568, NCT03815786: chronic kidney disease, NCT02704494: diabetic kidney disease, NCT03946176: hemodialysis patients |
| Antioxidants | ||||
| MitoQ | ROS scavenger and antioxidant which concentrates at the matrix in a mitochondrial membrane potential-dependent manner | Diabetic kidney disease (73, 164), cisplatin-induced acute kidney injury (165) | NCT02364648, NCT03960073 | NCT02364648: chronic kidney disease NCT03960073: HFpEF patients with and without chronic kidney disease |
| SkQ | Accumulates in mitochondria by penetrating planar phospholipid membranes | Mitochondrial DNA mutator mice (172), ischemia/reperfusion injury (166), gentamycin-induced nephrotoxicity (173) | N/A | N/A |
| Ubiquinone (coenzyme Q10, CoQ10) | Normalizes ATP production, attenuates mitochondria reactive oxidative species and decreases mitochondrial membrane potential | Diabetic kidney disease (167) | NCT04445779, NCT05422534, NCT03579693, NCT04972552, NCT00307996, NCT00908297, NCT05266794, NCT05214885, NCT01408680 | NCT04445779: acute kidney injury/failure NCT05422534: end stage renal disease NCT03579693: chronic kidney disease NCT04972552: kidney transplantation NCT00307996, NCT00908297, NCT05266794, NCT01408680 hemodialysis patients NCT05214885: clear cell renal cell carcinoma |
| Curcumin | Acts as an antioxidant and is responsible for altering mitochondrial dynamics and bioenergetics | 5/6 nephrectomy rats (169, 176), diabetic kidney disease (168) | NCT02369549, NCT03475017, NCT04413266, NCT03223883, NCT03935958, NCT03262363, NCT02494141, NCT04132648, NCT01285375, NCT01831193, NCT01225094, NCT05183737, NCT03019848, NCT04890704, NCT01906840 | NCT02369549, NCT03475017, NCT03223883, NCT03262363, NCT04132648, NCT05183737: chronic kidney disease NCT04413266: peritoneal dialysis NCT03935958, NCT01285375: kidney transplantation NCT02494141: autosomal dominant polycystic kidney, NCT01831193, NCT03019848: proteinuria NCT01225094, NCT04890704: acute kidney injury NCT01906840: end stage renal disease |
| Enhancement of Mitophagy and Autophagy | ||||
| Tat–beclin 1 | Inducer of autophagy, derived from a region of the autophagy protein, beclin 1 | Mice infected with chikungunya or West Nile virus (183) | N/A | N/A |
| Urolithin A | A gut microbial metabolite of ellagic acid and related compounds was reported to induce mitophagy | Cisplatin-induced AKI (186), two different mouse models of age-related decline in muscle function, as well as young rats and Caenorhabditis elegans (184) | N/A | N/A |
AKI: acute kidney injury, ATP: adenosine triphosphate, DRP1 GTPase: dynamin-related protein 1 guanosine triphosphatase, HFpEF: heart failure with preserved ejection fraction, HIV: human immunodeficiency viruses, Mdivi-1: mitochondrial division inhibitor 1, MPTP: mitochondrial permeability transition pore, NSAID: non-steroidal anti-inflammatory drugs, ROS: reactive oxygen species, SkQs: plastoquinone, SS-20: Szeto–Schiller peptide 20, SS-31: Szeto–Schiller peptide 31, TDZD-8: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione, 5HT1F: 5-hydroxytryptamine receptor 1F.