| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 1g |
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| Other Sizes |
Purity: ≥98%
| Targets |
AMPK GLUT4 AICAR; MOTS-c is a mitochondrial-derived peptide that acts as a metabolic hormone, primarily targeting skeletal muscle and fat. Its cellular mechanism involves inhibition of the folate-methionine cycle, leading to AICAR accumulation and AMPK activation. [1]
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| ln Vitro |
MOTS-c suppresses the folate cycle at the 5Me-THF level, which causes AICAR [5-aminoimidazole-4-carboxamide ribonucleotide] to build up. Nucleotide precursors, or NAD+, are likewise increased in cells by MOTS-c[1]. A mitochondrial signal called MOTS-c promotes the absorption of glucose by cells while inhibiting respiration. Rather of being broken down by glycolysis, the glucose that is taken up in response to MOTS-c is directed to the anabolic pentose phosphate pathway (PPP), which supplies carbon sources for the synthesis of purines. Furthermore, MOTS-c raises the amount of a β-oxidation intermediate, lowers intracellular levels of essential and non-essential fatty acids, and increases carnitine shuttles, which carry activated fatty acids into mitochondria for β-oxidation, all of which point to improved lipid utilization. Myocytes that consistently overexpress MOTS-c also show increased glucose uptake[1].
In myocytes that stably overexpress MOTS-c, increased glucose uptake was observed. [1] MOTS-c treatment in vitro increased cellular NAD⁺ levels and increased levels of carnitine shuttles (which transport activated fatty acids into mitochondria for β-oxidation), increased a β-oxidation intermediate, and reduced intracellular levels of essential and non-essential fatty acids, suggesting enhanced lipid utilization. [1] MOTS-c treatment in vitro routed glucose taken up to the anabolic pentose phosphate pathway (PPP), providing carbon sources for purine synthesis, rather than being metabolized through glycolysis. [1] |
| ln Vivo |
In mice given MOTS-c injections, skeletal muscle AMPK is activated and its downstream glucose transporter GLUT4 is elevated. In addition, MOTS-c might function as a possible mitochondrial signal that mediates a mitohormesis response brought on by exercise, promoting physiological adaptation and heightened exercise tolerance[1]. Skeletal muscle and fat seem to be MOTS-c's main target organs. As mice age, their levels of MOTS-c in their skeletal muscle and bloodstream decrease in tandem with the age-dependent emergence of insulin resistance. Age-dependent skeletal muscle insulin resistance is effectively reversed in older rats (12 mo.) by systemic injections that raise MOTS-c levels[1].
Acute systemic treatment of MOTS-c by intraperitoneal injection in mice significantly reduced non-fasting glucose levels and significantly improved glucose tolerance test (GTT) responses. [1] Hyperinsulinemic-euglycemic clamp studies demonstrated that MOTS-c regulates glucose homeostasis by targeting skeletal muscle to increase glucose clearance, but not the liver to reduce production. [1] In aged mice (12 months), systemic MOTS-c injections reversed age-dependent skeletal muscle insulin resistance. [1] In a high-fat diet (HFD)-induced mouse model of insulin resistance and obesity, MOTS-c prevented diet-induced obesity and insulin resistance, showing increased activation of AMPK and expression of its downstream glucose transporter in skeletal muscles. MOTS-c also caused a significant reduction in HFD-induced visceral fat and hepatic steatosis, and was associated with increased body heat production (thermal energy dissipation). HFD-fed mice treated with MOTS-c showed increased glucose utilization (higher respiratory exchange ratio, RER). [1] Fasting mice for 48 hours significantly reduced endogenous levels of MOTS-c in skeletal muscle and plasma. MOTS-c levels in mice decline with age in skeletal muscle and in circulation, concomitant with age-dependent development of insulin resistance. [1] |
| Animal Protocol |
Mouse Studies: Fasting studies: Mice were fasted for 48 hours, after which endogenous MOTS-c levels in skeletal muscle and plasma were measured. [1]
Acute treatment: Mice received intraperitoneal injections of MOTS-c to assess effects on non-fasting glucose levels and glucose tolerance test (GTT) responses. [1] Hyperinsulinemic-euglycemic clamp: This gold-standard technique was used to measure insulin action, specifically determining that MOTS-c increases glucose clearance by skeletal muscle rather than reducing hepatic glucose production. [1] Aged mouse study: Older mice (12 months) received systemic MOTS-c injections, which reversed age-dependent skeletal muscle insulin resistance. [1] High-fat diet (HFD) study: Mice fed a high-fat diet were treated with MOTS-c, which prevented diet-induced obesity and insulin resistance. Parameters measured included body weight, visceral fat, hepatic steatosis, body heat production, and respiratory exchange ratio (RER). [1] |
| References |
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| Additional Infomation |
MOTS-c (mitochondrial ORF of the twelve S c) is a 16-amino acid peptide encoded by a short open reading frame (sORF) within the mitochondrial 12S rRNA gene. It was identified in 2015 as a novel mitochondrial-derived peptide (MDP). [1]
MOTS-c is expressed in various tissues and circulates in plasma, acting as a mitochondrial hormone. Its primary target organs appear to be skeletal muscle and fat. [1] The cellular mechanism of MOTS-c involves inhibition of the folate-methionine cycle at the level of 5Me-THF, resulting in accumulation of AICAR (a well-defined AMPK activator) and increased NAD⁺ levels, which may involve SIRT1. [1] MOTS-c stimulates cellular glucose uptake while suppressing respiration (Crabtree effect), and glucose is routed to the pentose phosphate pathway (PPP) rather than glycolysis. [1] MOTS-c levels decline with age in both rodents and humans, correlating with age-dependent insulin resistance. A mitochondrial polymorphism (m.1382A>C) within the MOTS-c ORF, found in the D4b2 haplogroup associated with exceptional longevity in the Japanese population, causes a Lys14Gln amino acid change that may have functional implications. [1] MOTS-c has implications in obesity, diabetes, exercise, and longevity, representing a novel mitochondrial signaling mechanism to regulate metabolism. [1] |
| Molecular Formula |
C103H156N28O24S2
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| Molecular Weight |
2234.64
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| Exact Mass |
2174.111095
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| Related CAS # |
MOTS-c (human);1627580-64-6
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| PubChem CID |
155885767
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| Sequence |
H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH
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| SequenceShortening |
MRWQEMGYXFYPRKLR
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| Appearance |
White to off-white solid powder
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| LogP |
-3.9
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| Hydrogen Bond Donor Count |
31
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| Hydrogen Bond Acceptor Count |
29
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| Rotatable Bond Count |
73
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| Heavy Atom Count |
153
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| Complexity |
4510
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| Defined Atom Stereocenter Count |
16
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| SMILES |
CCC(C)C(C(=O)NC(CC1=CC=CC=C1)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)N3CCCC3C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(CC(C)C)C(=O)NC(CCCNC(=N)N)C(=O)O)NC(=O)C(CC4=CC=C(C=C4)O)NC(=O)CNC(=O)C(CCSC)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)N)NC(=O)C(CC5=CNC6=CC=CC=C65)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCSC)N
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| InChi Key |
WYTHCOXVWRKRAH-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
4-[[5-amino-2-[[2-[[2-[(2-amino-4-methylsulfanylbutanoyl)amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-oxopentanoyl]amino]-5-[[1-[[2-[[1-[[1-[[1-[[1-[2-[[1-[[6-amino-1-[[1-[(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
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| Synonyms |
MOTS-c (human); 1627580-64-6; MOTS-c Human Acetate
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
H2O :~6.25 mg/mL (~2.80 mM)
DMSO :~4 mg/mL (~1.79 mM) |
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.4475 mL | 2.2375 mL | 4.4750 mL | |
| 5 mM | 0.0895 mL | 0.4475 mL | 0.8950 mL | |
| 10 mM | 0.0447 mL | 0.2237 mL | 0.4475 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.
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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