Song KH

References (3)

Title : The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism - Oh_2023_Nat.Commun_14_5728
Author(s) : Oh M , Jang SY , Lee JY , Kim JW , Jung Y , Kim J , Seo J , Han TS , Jang E , Son HY , Kim D , Kim MW , Park JS , Song KH , Oh KJ , Kim WK , Bae KH , Huh YM , Kim SH , Han BS , Lee SC , Hwang GS , Lee EW
Ref : Nat Commun , 14 :5728 , 2023
Abstract : Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.
ESTHER : Oh_2023_Nat.Commun_14_5728
PubMedSearch : Oh_2023_Nat.Commun_14_5728
PubMedID: 37714840

Title : A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naive patients with type 2 diabetes - Yang_2015_Endocr.J_62_449
Author(s) : Yang HK , Min KW , Park SW , Chung CH , Park KS , Choi SH , Song KH , Kim DM , Lee MK , Sung YA , Baik SH , Kim IJ , Cha BS , Park JH , Ahn YB , Lee IK , Yoo SJ , Kim J , Park Ie B , Park TS , Yoon KH
Ref : Endocrine Journal , 62 :449 , 2015
Abstract : The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naive patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 +/- 9.77 years and 25.01 +/- 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 +/- 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 +/- 0.45 % and -0.51 +/- 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 +/- 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 +/- 1.25 mmol/L and -0.72 +/- 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 +/- 0.15 and -0.07 +/- 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.
ESTHER : Yang_2015_Endocr.J_62_449
PubMedSearch : Yang_2015_Endocr.J_62_449
PubMedID: 25819061

Title : Anagliptin and sitagliptin as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled, phase III clinical trial with a 28-week extension - Jin_2015_Diabetes.Obes.Metab_17_511
Author(s) : Jin SM , Park SW , Yoon KH , Min KW , Song KH , Park KS , Park JY , Park IB , Chung CH , Baik SH , Choi SH , Lee HW , Lee IK , Kim DM , Lee MK
Ref : Diabetes Obes Metab , 17 :511 , 2015
Abstract : We conducted a 24-week, multicentre, double-blind, randomized study with a 28-week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add-on to metformin in patients with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88). The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. The mean changes in HbA1c were -0.85 +/- 0.70% (p < 0.0001) for anagliptin and -0.83 +/- 0.61% (p < 0.0001) for sitagliptin, with a mean difference of -0.02% (95% confidence interval of difference, -0.22 to 0.18%). In both groups, the fasting proinsulin : insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were similar in each group. In conclusion, the non-inferiority of the efficacy of anagliptin to sitagliptin as an add-on therapy was established with regard to efficacy and safety.
ESTHER : Jin_2015_Diabetes.Obes.Metab_17_511
PubMedSearch : Jin_2015_Diabetes.Obes.Metab_17_511
PubMedID: 25523633