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MOTS-c (human)

Cat No.:V40974 Purity: ≥98%
MOTS-c (human) is a Mitochondria-derived peptide (MDP) which promotes biosynthesis of the endogenous AMP analog AICAR and consequently AMP-activated protein kinase (AMPK).
MOTS-c (human)
MOTS-c (human) Chemical Structure CAS No.: 1627580-64-6
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
MOTS-c (human) is a Mitochondria-derived peptide (MDP) which promotes biosynthesis of the endogenous AMP analog AICAR and consequently AMP-activated protein kinase (AMPK). Induces cellular and systemic glucose uptake and improves insulin sensitivity. Shown to prevent diet-induced obesity (DIO) in mice. Potential anti-obesity and anti-aging compound.
MOTS-c (human) is a mitochondria-derived peptide (MDP) that promotes the biosynthesis of the endogenous AMP analog AICAR and consequently AMP-activated protein kinase (AMPK). It induces cellular and systemic glucose uptake and improves insulin sensitivity. MOTS-c has been shown to prevent diet-induced obesity (DIO) in mice. The peptide has the amino acid sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg and the molecular formula C101H152N28O22S2 with molecular weight of 2174.59 g/mol. It is a potential anti-obesity and anti-aging compound.
Biological Activity I Assay Protocols (From Reference)
Targets
MOTS-c targets AMPK (AMP-activated protein kinase) through the AICAR pathway. The peptide promotes the biosynthesis of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an endogenous AMP analog, which in turn activates AMPK. AMPK is a key energy sensor that regulates glucose and lipid metabolism. By activating AMPK, MOTS-c induces cellular and systemic glucose uptake and improves insulin sensitivity. The peptide also has anti-inflammatory and neuroprotective effects, and can be used in the study of type 2 diabetes, traumatic brain injury, inflammatory diseases, and aging-related metabolic disorders.
ln Vitro
In vitro, MOTS-c has been shown to induce cellular glucose uptake and improve insulin sensitivity in various cell types. The peptide promotes the biosynthesis of AICAR and activates AMPK. MOTS-c has been studied for its effects on glucose and lipid metabolism, oxidative stress, and inflammation. These in vitro studies demonstrate the peptide's potential for treating metabolic disorders.
ln Vivo
In vivo, MOTS-c has been shown to prevent diet-induced obesity (DIO) in mice. The peptide induces systemic glucose uptake and improves insulin sensitivity. MOTS-c has also been studied for its effects on type 2 diabetes, traumatic brain injury, inflammatory diseases, and aging-related metabolic disorders. The peptide crosses the blood-brain barrier, allowing it to exert central effects. These in vivo studies support the potential of MOTS-c as a therapeutic agent for metabolic and aging-related diseases.
Enzyme Assay
In vitro receptor binding assays for MOTS-c are not typically performed as it is a peptide that works through intracellular signaling rather than cell surface receptors. However, binding studies with AMPK and other signaling molecules have been conducted. The peptide's effects on AICAR biosynthesis and AMPK activation are measured by ELISA or Western blot. Selectivity is assessed by testing the peptide against other AMPK activators or related pathways.
Cell Assay
In vitro cellular studies are conducted using various cell types including muscle cells, adipocytes, and hepatocytes. Cells are treated with MOTS-c at various concentrations (typically μM ranges) for defined time periods. Glucose uptake is measured using radioactive or fluorescent glucose analogs. Insulin sensitivity is assessed by measuring insulin-stimulated glucose uptake or signaling. AMPK phosphorylation is measured by Western blot. AICAR levels are measured by LC-MS/MS. Inflammatory markers and oxidative stress are also assessed.
Animal Protocol
In vivo animal experiments are performed using mouse models of diet-induced obesity (DIO), type 2 diabetes, and other metabolic disorders. Animals are administered MOTS-c via intraperitoneal injection or other routes at various doses. Body weight, food intake, and glucose tolerance are monitored. Insulin sensitivity is assessed by insulin tolerance tests or euglycemic-hyperinsulinemic clamps. Tissue samples are collected for analysis of AMPK activation, lipid metabolism, and inflammatory markers.
ADME/Pharmacokinetics
Pharmacokinetic properties of MOTS-c include its ability to cross the blood-brain barrier. The peptide has a molecular weight of 2174.59 g/mol and molecular formula C101H152N28O22S2. It appears as a white to off-white solid powder and has a LogP of -3.9. Storage at -20°C for powder is recommended. The peptide should be protected from moisture and light. The compound is supplied as a TFA salt.
Toxicity/Toxicokinetics
Toxicological data for MOTS-c are derived from preclinical studies. The compound is for research use only and not intended for human therapeutic applications. No significant toxicity has been reported at effective doses in animal studies. The peptide is naturally occurring and generally considered to have low toxicity. Standard safety precautions should be followed when handling the peptide. Long-term toxicity and carcinogenicity studies have not been conducted.
References

[1]. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci. 2022 Oct 9;23(19):11991.

[2]. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54.

[3]. The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test. Eur J Pharmacol. 2020 Mar 5;870:172909.

[4]. The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury. Sci Rep. 2023 Nov 13;13(1):19781.

Additional Infomation
MOTS-c (human) is a mitochondria-derived peptide (MDP) with the sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg. It promotes the biosynthesis of AICAR and activates AMPK, inducing cellular and systemic glucose uptake and improving insulin sensitivity. MOTS-c has been shown to prevent diet-induced obesity in mice and is a potential anti-obesity and anti-aging compound. The peptide crosses the blood-brain barrier and has anti-inflammatory and neuroprotective effects. It is used in research on type 2 diabetes, metabolic disorders, and aging-related diseases. Purity is ≥98%.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C101H152N28O22S2
Molecular Weight
2174.59199905396
Exact Mass
2174.111
CAS #
1627580-64-6
Related CAS #
MOTS-c(human) acetate
PubChem CID
146675088
Sequence
H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH . TFA Mitochondrial Open Reading Frame of the 12S rRNA-c MOTS3
SequenceShortening
MRWQEMGYIFYPRKLR
Appearance
White to off-white solid powder
LogP
-3.9
Hydrogen Bond Donor Count
31
Hydrogen Bond Acceptor Count
29
Rotatable Bond Count
73
Heavy Atom Count
153
Complexity
4510
Defined Atom Stereocenter Count
16
SMILES
S(C)CC[C@@H](C(NCC(N[C@@H](CC1C=CC(=CC=1)O)C(N[C@H](C(N[C@@H](CC1C=CC=CC=1)C(N[C@@H](CC1C=CC(=CC=1)O)C(N1CCC[C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(=O)O)CCCNC(=N)N)=O)CC(C)C)=O)CCCCN)=O)CCCNC(=N)N)=O)=O)=O)=O)[C@@H](C)CC)=O)=O)=O)NC([C@H](CCC(=O)O)NC([C@H](CCC(N)=O)NC([C@H](CC1=CNC2C=CC=CC1=2)NC([C@H](CCCNC(=N)N)NC([C@H](CCSC)N)=O)=O)=O)=O)=O
InChi Key
WYTHCOXVWRKRAH-LOKRTKBUSA-N
InChi Code
InChI=1S/C101H152N28O22S2/c1-7-57(4)83(96(148)126-76(50-58-19-9-8-10-20-58)92(144)127-78(52-60-30-34-63(131)35-31-60)97(149)129-46-18-27-79(129)95(147)122-69(25-16-44-112-100(107)108)86(138)118-67(23-13-14-42-102)87(139)124-74(49-56(2)3)91(143)123-73(98(150)151)26-17-45-113-101(109)110)128-94(146)75(51-59-28-32-62(130)33-29-59)116-81(133)55-115-85(137)72(41-48-153-6)121-90(142)71(37-39-82(134)135)119-89(141)70(36-38-80(104)132)120-93(145)77(53-61-54-114-66-22-12-11-21-64(61)66)125-88(140)68(24-15-43-111-99(105)106)117-84(136)65(103)40-47-152-5/h8-12,19-22,28-35,54,56-57,65,67-79,83,114,130-131H,7,13-18,23-27,36-53,55,102-103H2,1-6H3,(H2,104,132)(H,115,137)(H,116,133)(H,117,136)(H,118,138)(H,119,141)(H,120,145)(H,121,142)(H,122,147)(H,123,143)(H,124,139)(H,125,140)(H,126,148)(H,127,144)(H,128,146)(H,134,135)(H,150,151)(H4,105,106,111)(H4,107,108,112)(H4,109,110,113)/t57-,65-,67-,68-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,83-/m0/s1
Chemical Name
(4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-oxopentanoyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
H2O: ≥ 100 mg/mL (~46.0 mM)
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300:Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 0.4599 mL 2.2993 mL 4.5986 mL
5 mM 0.0920 mL 0.4599 mL 0.9197 mL
10 mM 0.0460 mL 0.2299 mL 0.4599 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration: mg/mL;

Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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