Gemigliptin (LC15-0444)
(Synonyms: 吉格列汀酒石酸盐,LC15-0444) 目录号 : GC33769
Gemigliptin (Zemiglo, LC15-0444) is a potent, selective and long-acting dipeptidyl peptidase 4 (DPP 4) inhibitor with a Ki of 7.25 nM. Gemigliptin shows at least >23,000-fold selectivity for DPP-4 over various proteases and peptidases, including DPP-8, DPP-9, and fibroblast activation protein (FAP)-α.
Cas No.:911637-19-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | The enzyme kinetic analysis of gemigliptin on DPP-4 is performed using a continuous spectrophotometric assay with the substrate Gly-Pro-pNA. Briefly, inhibition of DPP-4 activity is determined by measuring the absorbance (at 390 nm) resulting from the cleavage of the substrate Gly-Pro-pNA by the DPP-4 enzyme under steady-state conditions. Enzyme activity is defined as the slope (in mOD/ min) from 5 to 15 min. The inhibition pattern is evaluated using a Lineweaver-Burk plot, and the Ki is determined using a curve- fitting program[2]. |
Animal experiment: | Mice[1]Seven week-old male C57BL/KsJ-db/db mice and their lean littermates (db/þ, normal) are randomly assigned to three (n=10) groups. One group of db/db mice is orally administered gemigliptin (100 mg/kg body weight) and another group is administered the same amount of vehicle via oral gavage for 12 weeks. Non-diabetic littermates receive the same vehicle treatment. Blood glucose level and body weight are measured weekly[1]. |
References: [1]. Jung E, et al. Gemigliptin, a novel dipeptidyl peptidase-4 inhibitor, exhibits potent anti-glycation properties in vitro and in vivo. Eur J Pharmacol. 2014 Dec 5;744:98-102. | |
Gemigliptin (Zemiglo, LC15-0444) is a potent, selective and long-acting dipeptidyl peptidase 4 (DPP 4) inhibitor with a Ki of 7.25 nM. Gemigliptin shows at least >23,000-fold selectivity for DPP-4 over various proteases and peptidases, including DPP-8, DPP-9, and fibroblast activation protein (FAP)-α.
[1] Sung-Ho Kim, et al. Eur J Pharmacol. 2016 Oct 5;788:54-64. [2] Sung-Ho Kim, et al. Arch Pharm Res. 2013 Oct;36(10):1185-8.
| Cas No. | 911637-19-9 | SDF | |
| 别名 | 吉格列汀酒石酸盐,LC15-0444 | ||
| Canonical SMILES | O=C1N(C[C@@H](N)CC(N2CCC3=C(C(F)(F)F)N=C(C(F)(F)F)N=C3C2)=O)CC(F)(F)CC1 | ||
| 分子式 | C18H19F8N5O2 | 分子量 | 489.36 |
| 溶解度 | DMSO : ≥ 122.5 mg/mL (250.33 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0435 mL | 10.2174 mL | 20.4349 mL |
| 5 mM | 0.4087 mL | 2.0435 mL | 4.087 mL |
| 10 mM | 0.2043 mL | 1.0217 mL | 2.0435 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacological profiles of Gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivo
Eur J Pharmacol 2016 Oct 5;788:54-64.PMID:27298192DOI:10.1016/j.ejphar.2016.06.016.
Gemigliptin, a novel dipeptidyl peptidase (DPP)-4 inhibitor, is approved for use as a monotherapy or in combination therapy to treat hyperglycemia in patients with type 2 diabetes mellitus. In this study, we investigated the pharmacological profiles of gemigliptin in vitro and in vivo and compared them to those of the other DPP-4 inhibitors. Gemigliptin was a reversible and competitive inhibitor with a Ki value of 7.25±0.67nM. Similar potency was shown in plasma from humans, rats, dogs, and monkeys. The kinetics of DPP-4 inhibition by gemigliptin was characterized by a fast association and a slow dissociation rate compared to sitagliptin (fast on and fast off rate) or vildagliptin (slow on and slow off rate). In addition, gemigliptin showed at least >23,000-fold selectivity for DPP-4 over various proteases and peptidases, including DPP-8, DPP-9, and fibroblast activation protein (FAP)-α. In the rat, dog, and monkey, gemigliptin showed more potent DPP-4 inhibitory activity in vivo compared with sitagliptin. In mice and dogs, gemigliptin prevented the degradation of active glucagon-like peptide-1 by DPP-4 inhibition, which improved glucose tolerance by increasing insulin secretion and reducing glucagon secretion during an oral glucose tolerance test. The long-term anti-hyperglycemic effect of gemigliptin was evaluated in diet-induced obese mice and high-fat diet/streptozotocin-induced diabetic mice. Gemigliptin dose-dependently decreased hemoglobin A1c (HbA1c) levels and ameliorated β-cell damage. In conclusion, gemigliptin is a potent, long-acting, and highly selective DPP-4 inhibitor and can be a safe and effective drug for the long-term treatment of type 2 diabetes.
A Multicentre, Multinational, Open-Label, 52-Week Extension Study of Gemigliptin (LC15-0444) Monotherapy in Patients with Type 2 Diabetes Mellitus
Diabetes Metab J 2021 Jul;45(4):606-612.PMID:33081425DOI:10.4093/dmj.2020.0047.
The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (-0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was -0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was -0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.
Effect of renal impairment and haemodialysis on the pharmacokinetics of Gemigliptin (LC15-0444)
Diabetes Obes Metab 2014 Oct;16(10):1028-31.PMID:24641348DOI:10.1111/dom.12292.
This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end-stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66-fold (1.10, 1.49, 1.22 and 1.21-fold) increase of mean area under the time-plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non-HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure-response relationship. Impact of HD on the removal of gemigliptin was negligible.
Anti-inflammatory Effects of Empagliflozin and Gemigliptin on LPS-Stimulated Macrophage via the IKK/NF- κ B, MKK7/JNK, and JAK2/STAT1 Signalling Pathways
J Immunol Res 2021 Jun 2;2021:9944880.PMID:34124273DOI:10.1155/2021/9944880.
Background: Sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs whose anti-inflammatory properties have recently become useful in tackling metabolic syndromes in chronic inflammatory diseases, including diabetes and obesity. We investigated whether empagliflozin (SGLT2 inhibitor) and Gemigliptin (DPP-4 inhibitor) improve inflammatory responses in macrophages, identified signalling pathways responsible for these effects, and studied whether the effects can be augmented with dual empagliflozin and Gemigliptin therapy. Methods: RAW 264.7 macrophages were first stimulated with lipopolysaccharide (LPS), then cotreated with empagliflozin, Gemigliptin, or empagliflozin plus Gemigliptin. We conducted quantitative RT-PCR (qRT-PCR) to determine the most effective anti-inflammatory doses without cytotoxicity. We performed ELISA and qRT-PCR for inflammatory cytokines and chemokines and flow cytometry for CD80, the M1 macrophage surface marker, to evaluate the anti-inflammatory effects of empagliflozin and Gemigliptin. NF-κB, MAPK, and JAK2/STAT signalling pathways were examined via Western blotting to elucidate the molecular mechanisms of anti-inflammation. Results: LPS-stimulated CD80+ M1 macrophages were suppressed by coincubation with empagliflozin, Gemigliptin, and empagliflozin plus Gemigliptin, respectively. Empagliflozin and Gemigliptin (individually and combined) inhibited prostaglandin E2 (PGE2) release and COX-2, iNOS gene expression in LPS-stimulated RAW 264.7 macrophages. These three treatments also attenuated the secretion and mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, and proinflammatory chemokines, such as CCL3, CCL4, CCL5, and CXCL10. All of them blocked NF-κB, JNK, and STAT1/3 phosphorylation through IKKα/β, MKK4/7, and JAK2 signalling. Conclusions: Our study demonstrated the anti-inflammatory effects of empagliflozin and Gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and Gemigliptin treatment showed greater anti-inflammatory properties.
Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial
J Diabetes Res 2021 Oct 16;2021:7382620.PMID:34697593DOI:10.1155/2021/7382620.
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria, and vascular inflammation, especially in animal models. We evaluated the effects of a potent DPP4 inhibitor (Gemigliptin) on these processes among patients with diabetic kidney disease (DKD). Methods: This study employed a multicenter, prospective, randomized, placebo-controlled design. A total of 201 participants were enrolled and randomly assigned to one of two groups, one received treatment with 50 mg Gemigliptin daily along with standard care for diabetes mellitus for 6 months. The changes in the coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (eGFR), vascular calcification level, and tubular renal injury marker expression were evaluated at baseline and 6 months. Results: In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in the CAC score, CAVI, eGFR, and level of proteinuria over the 6 months of the study did not significantly differ between the Gemigliptin and control groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the Gemigliptin treatment group compared with the control group. No serious adverse events were observed during the study. Conclusion: Our study showed that Gemigliptin significantly improved the expression of renal tubular injury biomarkers and vascular calcification levels among patients with DKD; however, Gemigliptin did not affect renal function or coronary calcification compared with those observed in the control. A larger study with a longer follow-up is essential to verify these beneficial effects. Clinical Trials. This trial is registered with ClinicalTrials.Gov Identifier NCT04705506.