1. Epigenetics PI3K/Akt/mTOR Membrane Transporter/Ion Channel
  2. AMPK GLUT
  3. MOTS-c(human) acetate

MOTS-c (human) acetate is a blood-brain barrier-penetrating, mitochondrial-derived peptide that modulates the AMPK/PGC-1α pathway to enhance insulin sensitivity. MOTS-c (human) acetate inhibits the folate cycle and de novo purine synthesis, increases AICAR levels to activate AMPK, and then regulates the Nrf2/Keap1 antioxidant pathway and inhibits the NF-κB inflammatory pathway, while promoting mitochondrial biogenesis and energy metabolism. MOTS-c (human) acetate has the effects of improving glucose and lipid metabolism, anti-oxidative stress, anti-inflammatory and neuroprotection, and can be used in the study of type 2 diabetes, traumatic brain injury, inflammatory diseases and aging-related metabolic disorders.

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MOTS-c(human) acetate Chemical Structure

MOTS-c(human) acetate Chemical Structure

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Based on 1 publication(s) in Google Scholar

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Description

MOTS-c (human) acetate is a blood-brain barrier-penetrating, mitochondrial-derived peptide that modulates the AMPK/PGC-1α pathway to enhance insulin sensitivity. MOTS-c (human) acetate inhibits the folate cycle and de novo purine synthesis, increases AICAR levels to activate AMPK, and then regulates the Nrf2/Keap1 antioxidant pathway and inhibits the NF-κB inflammatory pathway, while promoting mitochondrial biogenesis and energy metabolism. MOTS-c (human) acetate has the effects of improving glucose and lipid metabolism, anti-oxidative stress, anti-inflammatory and neuroprotection, and can be used in the study of type 2 diabetes, traumatic brain injury, inflammatory diseases and aging-related metabolic disorders[1][2][3][4].

IC50 & Target[1]

AMPK

 

GLUT4

 

AICAR

 

In Vitro

Recent advances in high-resolution sequencing have led to the discovery of unique peptides derived from the mitochondrial genome. Eight peptides have been identified: humanin, the mitochondrial open reading frame of 12S tRNA-c (MOTS-c), and six small peptides (humanin-like peptides (SHLP1-6)). All of these peptides are released from mitochondria into the cytoplasm and are associated with extended lifespan and cell viability, reduced apoptosis, and other beneficial functions[1].
MOTS-c (human) acetate (10 μM; 24-72 h) activates AMPK (Thr172 phosphorylation) and the expression of downstream antioxidant proteins Nrf2 and Keap1, and inhibits the phosphorylation of MAPKs (ERK, JNK, P38) in HEK293 cells[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[2]

Cell Line: HEK293 cells
Concentration: 10 μM
Incubation Time: 24-72 h
Result: Significantly increased phosphorylation of AMPK at Thr172 and protein levels of Nrf2 and Keap1, while reducing phosphorylation of ERK, JNK, and P38.
Resulted activation of AMPK by densitometric quantification, with a 2-fold increase in p-AMPK/AMPK ratio compared to control.
Attenuated these effects by co-treatment with the AMPK inhibitor.
In Vivo

MOTS-c (human) (25-50 mg/kg; ip; once daily; 21 days) acetate can reduce neurological deficits and inhibit the HMGB1/TLR4/NF-κB inflammatory pathway in brain tissue in a traumatic brain injury model in male C57BL/6 mice[2].
MOTS-c (human) (5 mg/kg; ip; twice daily; 4 days) acetate can reduce inflammation associated with obesity and insulin resistance by recruiting IL-6 and TNF-α in an acute treatment model in male CD-1 mice[2].
MOTS-c (human) (50 mg/kg; ip; once a day; single dose) acetate can reduce paw licking time and inhibit the expression of spinal p-ERK/p-JNK/p-P38 and c-fos in the formalin inflammation model of male ICR mice, exerting anti-nociceptive and anti-inflammatory effects[3].
MOTS-c (human) (0.5 mg/kg; ip; once a day; 8 weeks) acetate can reduce fasting blood glucose, glycosylated serum protein and blood lipid levels, improve myocardial ultrastructural damage and activate myocardial AMPK/Nrf2 antioxidant pathway[4] in the male Sprague-Dawley rat type 2 diabetes model[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male C57BL/6 mice (6-8-week-old) with controlled-cortical impact (CCI)-induced traumatic brain injury model[2]
Dosage: 25 mg/kg, 50 mg/kg MOTS-c (human) (saline)
Administration: Intraperitoneal injection, once daily, for 21 days starting 1 hour post-injury
Result: At 50 mg/kg, MOTS-c reduced neurological severity scores (NSS) by 45% and improved rotarod performance (latency increased by 50%) compared to injured controls.
Brain tissue analysis showed reduced HMGB1 expression (30% decrease), TLR4/NF-κB pathway inhibition, and lower pro-inflammatory cytokines (TNF-α, IL-6) in the ipsilateral cortex.
OBB-NC formulation (3 mg/kg) showed comparable effects with enhanced BBB penetration.
Animal Model: Male ICR mice (25-30 g, 6-week-old) with Formalin-induced paw inflammation model[3]
Dosage: 50 mg/kg MOTS-c (human) (saline)
Administration: Intraperitoneal injection, 1 hour before formalin challenge, single dose
Result: Significantly reduced licking time in the late phase (phase II, 11-40 min) by 60% compared to vehicle controls.
Immunohistochemistry revealed decreased c-fos positive cells (40% reduction) in the spinal dorsal horn, with Western blot confirming suppressed phosphorylation of ERK (Thr202/Tyr204), JNK (Thr183/Tyr185), and P38 (Thr180/Tyr182) by 30-50%.
The AMPK inhibitor Compound C abolished these effects.
Animal Model: Male Sprague-Dawley rats (220-240 g, 7-week-old) with high-fat diet/streptozotocin-induced type 2 diabetes model[4]
Dosage: 0.5 mg/kg MOTS-c (human) (saline)
Administration: Intraperitoneal injection, once daily, for 8 weeks
Result: Significantly decreased fasting blood glucose (FBG) by 35%, HOMA-IR by 40%, and plasma triglycerides (TG)/total cholesterol (TC) by 25-30% compared to diabetic controls.
Reduced mitochondrial swelling and cristae damage, with increased SOD/GSH activity and upregulated p-AMPK, Nrf2, and Keap1 protein expression in the heart.
Combined with exercise, MOTS-c further enhanced glucose disposal and attenuated oxidative stress (MDA reduction by 50%).
Molecular Weight

2234.64

Formula

C103H156N28O24S2

Appearance

Solid

Color

White to off-white

Sequence

Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg

Sequence Shortening

MRWQEMGYIFYPRKLR

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Sealed storage, away from moisture

Powder -80°C 2 years
-20°C 1 year

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

H2O : 6.25 mg/mL (2.80 mM; Need ultrasonic)

DMSO : 4 mg/mL (1.79 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 0.4475 mL 2.2375 mL 4.4750 mL
5 mM --- --- ---
View the 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 (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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Purity & Documentation
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 (sealed storage, away from moisture). 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
DMSO / H2O 1 mM 0.4475 mL 2.2375 mL 4.4750 mL 11.1875 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
MOTS-c(human) acetate
Cat. No.:
HY-P2048A
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