Table 1.
Drugs already in clinical use targeting klotho.
| Drugs | Targets | References |
|---|---|---|
| Biguanide | ||
| Metformin | klotho protein↑ | (143, 144) |
| Dipeptidyl peptidase-4 (DPP-4) | ||
| Linagliptin | regulate FGF-23/klotho expression | (145) |
| Vildagliptin | klotho protein↑ | (146) |
| Sitagliptin | klotho protein↑ | (147) |
| Sodium-glucose co-transporter 2 (SGLT-2) inhibitors | ||
| Empagliflozine | increases or preserve klotho expression | (155, 156) |
| Canagliflozin | klotho protein↑, klotho mRNA↑ | (156) |
| Dapagliflozin | klotho protein↑, klotho mRNA↑ | (156) |
| Thiazolidinediones (TZDs) | ||
| Troglitazone | activates PPAR-γ, klotho protein↑, klotho mRNA↑ | (149) |
| Ciglitazone | activates PPAR-γ, klotho protein↑, klotho mRNA↑ | (149) |
| Pioglitazone | klotho protein↑, klotho mRNA↑ | (150) |
| Rosiglitazone | activates PPAR-γ, klotho protein↑, klotho mRNA↑ | (151) |
| Renin-angiotensin-aldosterone inhibitors | ||
| Losartan | klotho protein↑, klotho mRNA↑, preserve klotho expression | (45, 150) |
| Valsartan | klotho protein↑ | (159, 160) |
| Statins | ||
| Atorvastatin | preserve klotho expression | (44) |
| Pitavastatin | klotho protein↑, klotho mRNA↑, preserve klotho expression | (44, 164) |
| Simvastatin | klotho protein↑, klotho mRNA↑ | (166) |
| Fluvastatin | klotho mRNA↑ | (160) |
| Vitamin D Supplements | ||
| Vitamin D | klotho protein↑ | (168) |
| Calcitriol | klotho protein↑ | (170) |
| Paricalcitol | klotho protein↑ | (169) |
| mTOR inhibitor | ||
| Rapamycin | klotho protein↑, klotho mRNA↑ | (176, 177) |
| Nonspecific phosphodiesterase inhibitor | ||
| Pentoxifylline | klotho protein↑, preserve klotho expression | (180) |
| Phytotherapeutics | ||
| Cordycepin | klotho protein↑ | (181) |
| Resveratrol | klotho protein↑, klotho mRNA↑, mediated expression of klotho via SIRT1 | (182, 185, 188) |
| Astaxanthin | modulate klotho protein expression | (184) |
| Ligustilide | increases cleavage of full-length klotho by α-secretase | (183) |
| Ginseng | klotho protein↑, klotho mRNA↑ | (186, 187) |
| Tetrahydroxystilbene Glucoside | klotho protein↑ | (190) |
| Baicalin | regulates methylation of the klotho promoter | (191) |
| Curcumin | inhibits CpG hypermethylation of the klotho promoter | (192) |
| Dendrobium nobile Lindl. alkaloid | klotho protein↑ | (144) |
FGF-23, Fibroblast growth factor 23; peroxisome proliferator-activated receptor γ, PPAR-γ; Mammalian target of rapamycin, mTOR; silent information regulator factor 2-related enzyme 1, SIRT1.