Table 1.
Loss of function abnormalities caused by GPCR misfolding.
| Disease or Abnormality | GPCR | Examples of pharmacoperones tested in vitro and/or in vivo | Refs |
|---|---|---|---|
| Hypogonadotropic hypogonadism | GnRHR | IN3, IN30, Q89, A177775, TAK-013. | [21–27] |
| Nephrogenic diabetes insipidus | V2R | Satavaptan, relcovaptan, VPA-985, YM087, tolvaptan, OPC31260 | [28–34] |
| Retinitis pigmentosa | Rhodopsin | Retinoids (9-cis-retinal, 11-cis-retinal, 11-cis-7-ring retinal, vitamin A palmitate). | [35–40] |
| Congenital hypothyroidism | TSHR | ||
| Obesity | MC3R, MC4R | ML00253764 and compounds described in ref. | [41, 42, 65] |
| Ovarian failure | FSHR | Org41841 | [43] |
| Male pseudohermaphroditism | LHR | ||
| Familial hypocalciuric hypercalcemia | CaR | NPS R-568 | [44] |
| Red head color phenotype and propensity to skin cancer | MC1R | NBA-A | [45] |
| Familial glucocorticoid deficiency | MC2R | ||
| Hirschsprung’s disease | E-BR | ||
| Resistance to HIV-1 infection | CCR5 |
V2R: Vasopressin V2 receptor; GnRHR: Human gonadotropin-releasing hormone receptor; CaR: Calcium-sensing receptor; LHR: Luteinizing hormone receptor; FSHR: Follicle-stimulating hormone receptor; TSHR: Thyrotropin receptor; E-BR: Endothelin-B receptor; MC1R: Melanocortin-1 receptor; MC2R: Melanocortin-2 receptor [or adrenocorticotropin (ACTH) receptor]; MC3R: Melanocortin-3 receptor; MC4R: Melanocortin-4 receptor; CCR5: Chemokine receptor-5.