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

MOTS-c (human) is a blood-brain barrier-penetrating, mitochondrial-derived peptide that modulates the AMPK/PGC-1α pathway to enhance insulin sensitivity. MOTS-c (human) 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) 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)

MOTS-c (human) Chemical Structure

CAS No. : 1627580-64-6

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Based on 1 publication(s) in Google Scholar

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Description

MOTS-c (human) is a blood-brain barrier-penetrating, mitochondrial-derived peptide that modulates the AMPK/PGC-1α pathway to enhance insulin sensitivity. MOTS-c (human) 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) 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

GLUT4

 

AMPK

 

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) (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) 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) 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) 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) 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 (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 (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 (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

2174.59

Formula

C101H152N28O22S2

CAS No.
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 : ≥ 100 mg/mL (45.99 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 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
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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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.
Calculation results:
Working solution concentration: mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation

Purity: 99.90%

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
H2O 1 mM 0.4599 mL 2.2993 mL 4.5986 mL 11.4964 mL
5 mM 0.0920 mL 0.4599 mL 0.9197 mL 2.2993 mL
10 mM 0.0460 mL 0.2299 mL 0.4599 mL 1.1496 mL
15 mM 0.0307 mL 0.1533 mL 0.3066 mL 0.7664 mL
20 mM 0.0230 mL 0.1150 mL 0.2299 mL 0.5748 mL
25 mM 0.0184 mL 0.0920 mL 0.1839 mL 0.4599 mL
30 mM 0.0153 mL 0.0766 mL 0.1533 mL 0.3832 mL
40 mM 0.0115 mL 0.0575 mL 0.1150 mL 0.2874 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)
Cat. No.:
HY-P2048
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