MID-35

MID-35 (Myostatin Inhibitory D-Peptide)

MID-35 is a synthetic, 16-amino-acid retro-inverso D-peptide designed as a selective inhibitor of myostatin (Growth Differentiation Factor 8, GDF-8). By utilizing a retro-inverso configuration—reversing the amino acid sequence and employing D-form residues—MID-35 maintains the precise spatial orientation required for myostatin binding while achieving significant resistance to proteolytic degradation. This structural design makes it a specialized tool for studying myostatin-mediated signaling and muscle growth regulation in controlled in vitro and in vivo laboratory models.

Technical Specifications

Mechanism of Action & Research Context

Myostatin acts as a negative regulator of skeletal muscle growth by signaling through the activin receptor type IIB (ActRIIB). This process recruits type I receptors (ALK4/ALK5) and triggers downstream Smad2/3 phosphorylation, which inhibits myogenic gene transcription.

• Selective Inhibition: MID-35 binds directly to the myostatin/activin type I receptor interface, effectively blocking Smad2/3 signaling activation.

• Selectivity Profile: Unlike decoy receptor strategies or broad-spectrum inhibitors (e.g., follistatin), MID-35 exhibits high selectivity for myostatin, minimizing neutralization of other TGF-β superfamily ligands like activin A or BMP9/10.

• Enzymatic Stability: The D-amino acid configuration provides superior resistance to standard proteolytic enzymes compared to conventional L-peptide inhibitors, enhancing stability in research applications.

Research Applications

MID-35 serves as a high-potency probe for investigating muscle atrophy, sarcopenia, and myostatin-mediated signaling pathways.

Primary fields of laboratory investigation include:

• Myogenic Signaling Research: Evaluating the modulation of muscle growth and atrophy gene expression (e.g., MyoD, Atrogin-1, MuRF-1).

• Cachexia Models: Studying the alleviation of skeletal muscle atrophy in disease-state models (e.g., cancer cachexia) and synergy with other metabolic modulators.

• Non-Invasive Delivery Systems: Investigating transdermal delivery technologies, such as iontophoresis, for peptide transport into skeletal muscle.

• Structure-Activity Relationship (SAR): Comparative analysis of retro-inverso vs. L-peptide configurations in myostatin binding potency.

Storage & Handling Guidelines

To maintain the chemical stability and experimental viability of the peptide:

• Long-Term Storage: Store lyophilized vials at -20°C, protected from light and moisture.

• Reconstituted Solutions: Store at 2–8°C. Use within 14 days and minimize freeze-thaw cycles by aliquoting as needed.

• Reconstitution: Recommended for use with bacteriostatic water or sterile 0.9% saline.

• Handling: Utilize sterile laboratory techniques to prevent contamination.

Research Use Disclaimer

Research Use Only Disclaimer: This product is developed and distributed strictly as a Research Use Only (RUO) laboratory reference chemical intended exclusively for non-clinical analytical and scientific investigation. It is not an FDA-approved drug, medical treatment, dietary supplement, or food ingredient, and is strictly prohibited for human or animal consumption. Kimera Chems supplies this high-purity research material solely to qualified institutions and professional investigators for authorized laboratory research purposes.

Key Preclinical Literature

• Takayama K, et al. (2022) Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice. ACS Med. Chem. Lett. 13(3):492–498.

• Hanada K, et al. (2022) Combination therapy with anamorelin and a myostatin inhibitor is advantageous for cancer cachexia in a mouse model. Cancer Sci. 113(11):3766–3779.

• Michiue K, et al. (2023) Increasing Skeletal Muscle Mass in Mice by Non-Invasive Intramuscular Delivery of Myostatin Inhibitory Peptide by Iontophoresis. Pharmaceuticals. 16(3):397.