MK3102
(Synonyms: 奥格列汀(MK-3102),MK-3102) 目录号 : GC17012
MK3102 (Omarigliptin)是一种新型的每周一次的二肽基肽酶-4 (DPP-4)抑制剂(IC50: 2.2 nM),用于治疗2型糖尿病。
Cas No.:1226781-44-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment [1]: | |
Cell lines |
PC12 cells |
Preparation Method |
PC12 cells were treated with MK3102 at a series of concentrations in culture media containing low serum (1% FBS, 1% HS, 100 IU/mL penicillin, and 100 µg/mL streptomycin) for 24 h. Control cells were treated with the same media containing low serum and an equivalent volume of DMSO (0.5%). The protective effects of MK3102 against 6-OHDA- or rotenone-induced toxicity in PC12 cells were evaluated. Briefly, cells were pretreated with MK3102 at various concentrations for 4 h and subsequently exposed to 6-OHDA (50 µM) or rotenone (1 µM) for 24 h. The effect of ZnPP, an HO-1 inhibitor, on the protective effects of MK3102 against 6-OHDA- or rotenone-induced toxicity was evaluated. In brief, the cells were pretreated with 0.2 µM ZnPP for 30 min and exposed to MK3102 for 4 h. Then, 6-OHDA or rotenone was added at the final concentrations of 50 and 1 µM, respectively, and incubated for 24 h. |
Reaction Conditions |
0-100µM for 24 hours; 0-50µM pretreat for 4 hours |
Applications |
Pretreatment with MK3102 presented a significant reversal of the 6-OHDA-induced toxicity at concentrations of 30 and 50 µM. |
Animal experiment [2]: | |
Animal models |
Male C57BL/6 mice |
Preparation Method |
The 24 mice (6- to 8-week-old) were divided into 4 groups: the vehicle, MK3102, LPS, and LPS + MK3102 groups. The animals were orally administered with either vehicle (saline) or MK3102 at 5 mg/kg/d for 15 days. On the last day, the animals in the LPS and the LPS + MK3102 groups were intraperitoneally injected with LPS (5 mg/kg). The control and the MK3102 groups were intraperitoneally injected with the same amounts of saline. |
Dosage form |
5 mg/kg/d, oral, for 15 days. |
Applications |
Compared with the vehicle group, the expression levels of TNF-α, IL-6, and IL-8 were elevated significantly in the brain of LPS stimulated mice but were greatly suppressed by the coadministration of MK3102. |
References: [1]: Gouda NA, Cho J. Omarigliptin Mitigates 6-Hydroxydopamine-or Rotenone-Induced Oxidative Toxicity in PC12 Cells by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Actions. Antioxidants. 2022 Sep 28;11(10):1940. |
MK3102 (Omarigliptin) is a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor (IC50: 2.2 nM) developed for the treatment of type 2 diabetes [1,2]. MK3102 crossed the blood brain barrier (BBB) due to its low molecular weight and lipophilic properties [3].
MK3102 (3, 10, 30, and 50 µM, 4 h) pretreated PC12 cells were attenuated 6-OHDA (50 µM, 24h) - or rotenone (1 µM, 24h) - induced cytotoxicity. MK3102 inhibited the 6-OHDA- or rotenone-induced production of intracellular ROS in PC12 cells [4]. MK3102 decreased the 6-OHDA- and rotenone-induced IκBα phosphorylation and nuclear translocation of NF-κB, resulting in reduced production of the inflammatory mediator NO and iNOS expression [4]. MK3102 suppressed the release of HMGB-1, and decreased the permeability of endothelial monolayer in bEnd.3 brain endothelial cells [1].
MK3102 has a long half-life (rat, 11 h; dog, 22 h) and lower clearance (rat, 1.1 mL min-1 kg-1; dog, 0.9 mL min-1 kg-1) in preclinical species [5]. Concentration of MK3102 in rats' plasma (5 mg/kg, after 2 h, p.o) were found to be 2688.79 ng/mL, MK3102 crossed the BBB after the oral administration showing concentration of 621.75 ng/g in brain tissue. Intra-nasal administration of OG showed significant higher brain/plasma concentration ratio of 0.76 enhancing the ratio by 3.3 folds compared to the oral route [3]. MK3102 (5 mg/kg/d) suppressed the release of inflammatory factors in the brains of LPS-Stimulated mice and protected the BBB integrity destroyed by LPS stimulation [1].
References:
[1]. Du H, Wang S. Omarigliptin Mitigates Lipopolysaccharide-Induced Neuroinflammation and Dysfunction of the Integrity of the Blood-Brain Barrier. ACS Chemical Neuroscience. 2020 Nov 25;11(24):4262-9.
[2]. Hussain H, Abbas G, Green IR, Ali I. Dipeptidyl peptidase IV inhibitors as a potential target for diabetes: patent review (2015-2018). Expert opinion on therapeutic patents. 2019 Jul 3;29(7):535-53.
[3]. Ayoub BM, Mowaka S, Safar MM, Ashoush N, Arafa MG, Michel HE, Tadros MM, Elmazar MM, Mousa SA. Repositioning of omarigliptin as a once-weekly intranasal anti-parkinsonian agent. Scientific Reports. 2018 Jun 12;8(1):8959.
[4]. Gouda NA, Cho J. Omarigliptin Mitigates 6-Hydroxydopamine-or Rotenone-Induced Oxidative Toxicity in PC12 Cells by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Actions. Antioxidants. 2022 Sep 28;11(10):1940.
[5]. Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y, Krueger D, Bak A. Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes.
Cas No. | 1226781-44-7 | SDF | |
别名 | 奥格列汀(MK-3102),MK-3102 | ||
化学名 | (2R,3S,5R)-2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)pyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)tetrahydro-2H-pyran-3-amine | ||
Canonical SMILES | CS(N1C=C2CN([C@](CO3)([H])C[C@@](N)([H])[C@@]3([H])C4=C(F)C=CC(F)=C4)CC2=N1)(=O)=O | ||
分子式 | C17H20F2N4O3S | 分子量 | 398.43 |
溶解度 | ≥ 17.15mg/mL in DMSO | 储存条件 | Store at -20°C |
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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。 |
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1 mg | 5 mg | 10 mg |
1 mM | 2.5099 mL | 12.5493 mL | 25.0985 mL |
5 mM | 0.502 mL | 2.5099 mL | 5.0197 mL |
10 mM | 0.251 mL | 1.2549 mL | 2.5099 mL |
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