A DPP-4 inhibitor
Gemigliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4; IC50 = 0.01 ?M).1 It is selective for DPP-4 over DPP-8, DPP-9, and fibroblast activation protein-α (FAP-α; IC50s = 277.28, 233.72, 418.43 ?M, respectively). Gemigliptin inhibits DPP-4 activity in isolated human, rat, dog, and monkey plasma (IC50s = 11.5, 14.5, 14.5, and 14 nM, respectively). It scavenges methylglyoxal in vitro and inhibits advanced glycation end product (AGE) formation between BSA and methylglyoxal and cross-linking of AGE-BSA with rat tail tendon collagen (IC50s = 1.15, 11.69, and 1.39 mM, respectively).2 Gemigliptin (100 mg/kg) reduces the levels of circulating AGE and red blood cell IgG content in a db/db mouse model of diabetes when administered for 12 weeks. It decreases blood glucose and hemoglobin A1c (HbA1c) levels and reduces pancreatic β-cell damage in a dose-dependent manner in a mouse model of diabetes induced by a high-fat diet and streptozotocin .1 Gemigliptin also induces cytotoxicity in SW1736 and TPC-1 human thyroid cancer cells.3,4 Formulations containing gemigliptin have been used in the treatment of type 2 diabetes.
1.Kim, S.-H., Jung, E., Yoon, M.K., et al.Pharmacological profiles of gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivoEur. J. Pharmacol.78854-64(2016) 2.Jung, E., Kim, J., Kim, S.H., et al.Gemigliptin, a novel dipeptidyl peptidase-4 inhibitor, exhibits potent anti-glycation properties in vitro and in vivoEur. J. Pharmacol.74498-102(2014) 3.Kim, S.H., Kang, J.G., Kim, C.S., et al.Gemigliptin, a novel dipeptidyl peptidase-IV inhibitor, exerts a synergistic cytotoxicity with the histone deacetylase inhibitor PXD101 in thyroid carcinoma cellsJ. Endocrinol. Invest.41(6)677-689(2018) 4.Kim, S.H., Kang, J.G., Kim, C.S., et al.Synergistic cytotoxicity of the dipeptidyl peptidase-IV inhibitor gemigliptin with metformin in thyroid carcinoma cellsEndocrine59(2)383-394(2018)
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