TABLE 1.
Proteins classified as “Tclin” and their targeting drug, including mode of action.
| Protein/Gene | Function of protein, especially in the cochlea | Drugs | Mode of action |
|---|---|---|---|
| Carbonic anhydrase 3 (CA3) | Function: Reversible hydration of carbon dioxide | Acetazolamide, Ethoxzolamide, Imatinib, Nilotinib, Lacosamide | All approved drugs are inhibitors |
| Cochlea: Facilitating mitochondrial ATP synthesis, detoxifying free radicals, HCO3—secretion into the endolymph | |||
| Thymidine phosphorylase (TYMP) | Function: Reversible phosphorolysis of thymidine, angiogenic factor | Tipiracil | Inhibitor |
| Cochlea: Associated with MNGIE-syndrome (Hearing loss in 61%) | |||
| Glucosylceramidase (GBA) | Function: Glycolipid metabolism, hydrolysis of glucosylceramidase | Ambroxol | Metabolite of Bromhexine that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride |
| Cochlea: Associated with Gaucher disease (case reports of hearing loss) | |||
| Isocitrate dehydrogenase [NADP] cytoplasmic (IDH1) | Function: Catalyses the oxidative decarboxylation of isocitrate to 2-oxoglutarate | Ivosidenib | Inhibitor |
| Cochlea: Protects inner ear from oxidative stress during K + Recycling, participates in K + -Transport. Downregulated in age related hearing loss and by lead exposure | |||
| ATP-citrate synthase (ACLY) | Function: Primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. In nervous tissue it may be involved in the biosynthesis of acetylcholine | Bempedoic acid | Inhibitor |
| Cochlea: Either hair cell specific or strongly upregulated in hair cells compared to non-sensory cells | |||
| Lysosomal alpha-glucosidase (GAA) | Function: Essential for the degradation of glycogen in lysosomes | Miglustat | Inhibitors: Miglustat, Miglitol, Voglibose |
| Cochlea: Mutations are associated with Pompe’s disease (associated with hearing loss in 21%) | Miglitol | ||
| Migalastat | Activator: Migalastat | ||
| Voglibose | |||
| Alcohol dehydrogenase 1B | Function: Oxidoreductase in ethanol metabolism Cochlea: No information available | Fomepizol | Inhibitor |
| Janus Kinase 1 (JAK1) | Function: Tyrosine kinase that phosphorylates STAT proteins, involved in interferon signal transduction | Sunitinib | All approved drugs are inhibitors |
| Cochlea: Regulates proliferation in support cells after hair cell death, STAT3 signalling is important during cochlear hair cell differentiation, downregulated by cisplatin treatment | Nintedanib | ||
| Tofacitinib | |||
| Ruxolitinib | |||
| Fedratinib | |||
| Baricitinib | |||
| Upadacitinib | |||
| Aldehyde dehydrogenase, mitochondrial (ALDH2) | Function: Oxidoreductase in the major oxidative pathway of alcohol metabolism | Disulfiram | Inhibitor |
| Cochlea: Expressed in surrounding cells |