MK3102 (Synonyms: Omarigliptin) |
Catalog No.GC17012
One-Click Copy Product Info
|
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.
Products are for research use only. Not for human use. We do not sell to patients.
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]: | |
|
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. | |
| Cas No. | 1226781-44-7 | SDF | |
| Synonyms | Omarigliptin | ||
| Chemical Name | (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 | ||
| Formula | C17H20F2N4O3S | M.Wt | 398.43 |
| Solubility | ≥ 17.15mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5099 mL | 12.5493 mL | 25.0985 mL |
| 5 mM | 502 μL | 2.5099 mL | 5.0197 mL |
| 10 mM | 251 μL | 1.2549 mL | 2.5099 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
-
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
Average Rating: 5 (Based on Reviews and 36 reference(s) in Google Scholar.)