Tiopronin

Tiopronin (trade name Thiola) is a prescription thiol drug used to control the rate of cystine precipitation and excretion in the disease cystinuria. Due to the rarity of the disorder, tioronin falls under the classification of an orphan drug. (In Vitro) :In in vitro Von Hippel-Lindau protein binding assay, the inhibitory effect of Tiopronin (NMPG) on HPH-2 was attenuated by escalating dose of ascorbate but not 2-ketoglutarate, cofactors of the enzyme. (In Vivo) :Tiopronin (NMPG) alleviates colonic injury and effectively lowered myeloperoxidase activity. Moreover, NMPG substantially attenuates expression of pro-inflammatory mediators in the inflamed colon. NMPG induces hypoxia-inducible factor-1α (HIF-1α) in human colon carcinoma cells, leading to elevated secretion of vascular endothelial growth factor (VEGF), a target gene product of HIF-1 involved in ulcer healing of gastrointestinal mucosa. NMPG induces HIF-1α occurred by inhibiting HIF prolyl hydroxylase-2 (HPH-2), an enzyme that plays a major role in negatively regulating HIF-1α protein stability.