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.
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.
| Cell experiment [1]: | |
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Cell lines |
PC12 cells |
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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. |
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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]: | |
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Animal models |
Male C57BL/6 mice |
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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. |
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Dosage form |
5 mg/kg/d, oral, for 15 days. |
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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. |
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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. | |
| 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 |
| 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 | 2.5099 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 |
| 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。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Related Biological Data
MK3102 reduced hematoma size and improved functional recovery after ICH.(C) Representative microphotographs of Nissl staining in the perihematomal area.The small black squares in the coronal section of brain indicate the area where microphotograph was taken.
For the MK3102 treatment, the MK3102 (Glpbio, USA) was dissolved in 10% DMSO and was given (7 mg/kg/day) via gavage starting from 1 hour after collagenase injection.
J Inflamm Res (2023): 2535-2548. PMID: 37342770 IF: 4.6307 -
Related Biological Data
MK3102 reduces the neurotoxicity of hemin in cultured primary cortical neurons in a concentrationdependent manner. (B) The toxicity of 20 μM of hemin was attenuated by MK3102 in a concentration-dependent manner.
For the MK3102 treatment, the MK3102 (Glpbio, USA) was dissolved in 10% DMSO and administrated (7 mg/kg/day) by gastric injection starting from 1 h after surgery.
Sci Rep-Uk 13.1 (2023): 14339. PMID: 37658227 IF: 4.6