MARY1
Based on 1 Customer Validation
MARY1 is a selective 5-HT2BR antagonist with an IC50 of 380 nM and a Ki of 764 nM (human 5-HT2BR). MARY1 induces renal mitochondrial biogenesis (MB) and enhances renal mitochondrial function by increasing mitochondrial respiratory capacity, mitochondrial protein levels, and mitochondrial number in renal proximal tubular cells (RPTCs). MARY1 induces MB through 5-HT2BR and dual PI3K/AKT and RAS/MEK/ERK cell signaling pathways in RPTCs. MARY1 can be used to study renal diseases associated with metabolic and mitochondrial dysfunction.
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- Purity : 99.46%
- 화학식: C18H17F3N4O2
- 분자량:378.35
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
5-HT2B Receptor 380 nM (IC50) |
human 5-HT2B Receptor 761 nM (Ki) |
In Vitro
MARY1 binds with moderate affinity to 5-HT2BR, with no significant binding to 5-HT2A/2C receptors[1].
MARY1 (1 nM-1 μM, 24 h) increase maximal mitochondrial respiration in RPTCs[1].
MARY1 (1 nM, 24 h) enhances cellular mitochondrial maximal respiration, upregulates key genes responsible for mitochondrial bioenergetics, and increases the number of mitochondria in RPTCs[1].
MARY1 increases PGC-1α expression in RPTCs treated with scRNA but not in those treated with siRNA[1].
MARY1 (1 nM, 20 min) induces MB through 5-HT2BR and dual PI3K/AKT and RAS/MEK/ERK cell signaling pathways in RPTCs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:RPTCs
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Concentration:1 nM
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Incubation Time:24 h
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Result:Increased the protein levels of mitochondrial-specific genes in RPTCs, including carnitine palmitoyltransferase 1A (CPT1A), acyl-CoA synthetase medium-chain family member 2A (ACSM2A), and NADH dehydrogenase [ubiquinone] 1β subcomplex subunit 8 (NDUFB8).
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Cell Line:RPTCs
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Concentration:1 nM
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Incubation Time:20 min
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Result:Increased pAKT (S473) and pFOXO1 (S256) .
Activated RAS GTPase and activated phosphorylation of extracellular signal-regulated kinase (pERK) at the threonine 202/tyrosine 204 (T202/Y204) position.
Parmacokinetics
| Species | Dose | Route | AUC0-t | Cmax | Tmax | T1/2 | Vz-F_obs | ClF_obs |
|---|---|---|---|---|---|---|---|---|
| Mice | 0.3 mg/kg | i.v. | 19.8 ng·h/mL | 11.9 ng/mL | 0.5 h | 1.22 h | 26785.2 mL/kg | 15145.3 mL/h/kg |
| Mice | 0.3 mg/kg | s.c. | 22.9 ng·h/mL | 27.2 ng/mL | 0.5 h | 1.16 h | 22043.6 mL/kg | 13074.6 mL/h/kg |
In Vivo
MARY1 (0.3 mg/kg, i.p.,once) induces MB in the renal cortex in male C57BL/6NCrl mice[1].
MARY1 (0.15-0.3 mg / kg, i.p., once) induces MB in the renal cortex in Male SD rats[1].
MARY1 (0.15-15 mg/kg, i.p., once a day, 4 weeks) does not cause any death or organ and weight abnormalities in male SD rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6NCrl mice 8 weeks of age and weighing ∼20-25 g[1]
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Dosage:0.3 mg/kg
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Administration:i.p.,once
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Result:Increased PGC-1α and sirtuin 1 (SIRT1) mRNA, and mtDNA content (DLOOP and mtND1) in the renal cortex, with no effect on mitochondrial transcription factor A.
Upregulated nuclear (3.46-fold), but not cytosolic PGC-1α in the renal cortex.
Increased ACSM2A (1.75-fold), NDUFB8 (1.52-fold), and stearoyl-CoA desaturase 1 (SCD1; 1.65-fold) proteins.
Increased complex I (NDUFB8) and II (SDHB) proteins of the mitochondrial electron transport chain, with no changes in complexes III (UQCRC2), IV (MTCO1), or V (ATP5A)
Increased mitochondrial fission proteins mitochondrial fission factor (Mff; 1.79-fold) and dynamin-related protein 1 (Drp1; 2.01-fold) in the mouse renal cortex, but not mitochondrial fusion proteins mitofusin 1 (MFN1) and 2 (MFN2), and did not alter TFAM protein levels.
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Animal Model:Male SD rats(weighing 250-300 g) [1]
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Dosage:0.15 mg/kg, 0.3 mg/kg
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Administration:i.p., once
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Result:Increased PGC-1α protein levels in the renal cortex at both doses.
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Animal Model:Male SD rats(weighing 250-300 g) [1]
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Dosage:0.15 mg/kg, 1.5mg/kg, 15 mg/kg
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Administration:i.p., once a day, 4 weeks
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Result:Did not cause any death or organ and weight abnormalities.
Chemical Information
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Appearance Solid
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분자량 378.35
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화학식 C18H17F3N4O2
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SMILES
FC1=C(C(F)=CC(F)=C1)C(NC2=NC(C(N3CCN(CC3)C)=O)=CC=C2)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 100 mg/mL (264.31 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 5 mg/mL (13.22 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (13.22 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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Mitochondrial membrane-potential fluorescent assay
Mitochondrial membrane potential fluorescent assays estimate ΔΨm in living cells using lipophilic cationic dyes such as TMRM, TMRE, rhodamine 123, and JC-1, which accumulate in mitochondria according to membrane polarization; loss of signal after FCCP or CCCP treatment is interpreted as mitochondrial depolarization. TMRM/TMRE and rhodamine 123 are commonly used for semi-quantitative live-cell microscopy or flow cytometry, while JC-1 can report a shift from red aggregate fluorescence to green monomer fluorescence during depolarization; interpretation requires controls because dye concentration, quenching mode, cell type, dye efflux, and mitochondrial mass can affect fluorescence independently of ΔΨm.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
순도&문서
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.6431 mL | 13.2153 mL | 26.4306 mL | 66.0764 mL |
| 5 mM | 0.5286 mL | 2.6431 mL | 5.2861 mL | 13.2153 mL | |
| 10 mM | 0.2643 mL | 1.3215 mL | 2.6431 mL | 6.6076 mL | |
| 15 mM | 0.1762 mL | 0.8810 mL | 1.7620 mL | 4.4051 mL | |
| 20 mM | 0.1322 mL | 0.6608 mL | 1.3215 mL | 3.3038 mL | |
| 25 mM | 0.1057 mL | 0.5286 mL | 1.0572 mL | 2.6431 mL | |
| 30 mM | 0.0881 mL | 0.4405 mL | 0.8810 mL | 2.2025 mL | |
| 40 mM | 0.0661 mL | 0.3304 mL | 0.6608 mL | 1.6519 mL | |
| 50 mM | 0.0529 mL | 0.2643 mL | 0.5286 mL | 1.3215 mL | |
| 60 mM | 0.0441 mL | 0.2203 mL | 0.4405 mL | 1.1013 mL | |
| 80 mM | 0.0330 mL | 0.1652 mL | 0.3304 mL | 0.8260 mL | |
| 100 mM | 0.0264 mL | 0.1322 mL | 0.2643 mL | 0.6608 mL |
MARY1 Related Classifications
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