Insulin 0143-0406 (LYS)

Insulin 0143-0406 (LYS) is an investigational long-acting basal insulin analogue under clinical development for type 2 diabetes treatment. This molecule is a modified human insulin with a lipophilic moiety, likely a long-chain fatty acid, conjugated at a specific lysine (LYS) residue. This acylation enhances binding to albumin in the bloodstream, considerably extending the half-life and enabling less frequent dosing compared to standard basal insulins.

Appearance:

• Presumed clear, colorless solution for subcutaneous injection, similar to other insulin analogues.

Source:

• Produced via recombinant DNA technology in expression systems such as Saccharomyces cerevisiae or E. coli.

• The insulin is chemically modified post-expression with the lipophilic moiety.

Molecular Weight:

• Higher than unmodified human insulin (~5.8 kDa) due to the fatty acid attachment. Exact weight varies with modification size.

Structure:

• Human insulin amino acid sequence modified at a lysine residue by covalent linkage to a fatty acid or similar lipophilic group on the epsilon-amino side chain, critical for its pharmacological profile.

Biological Activity:

• Stimulates glucose uptake and inhibits hepatic glucose production.

• Binds to insulin receptors on target tissues such as muscle, liver, and adipose tissue.

• The lysine modification prolongs duration of insulin action, facilitating extended dosing intervals.

Purity and Microbial Contamination:

• Purity typically ≥95% by HPLC, meeting rigorous pharmaceutical-grade standards.

• Sterility and endotoxin levels regulated and confirmed by standard assays.

Identity and Quality Control:

• Mass spectrometry confirms correct molecular weight and modification profile.

• Amino acid analysis and peptide mapping verify amino acid sequence and site-specific modification.

• HPLC and SDS-PAGE used for purity and aggregation assessments.

• Bioassays measure receptor binding and metabolic activity.

Shelf Life and Storage

Applications

• Investigational treatment for basal insulin replacement in type 2 diabetes, focusing on improved patient adherence via reduced injection frequency.

Key Characteristics

• Human insulin analogue with site-specific acylation at lysine for albumin binding.

• Designed as an ultra-long-acting insulin allowing less frequent dosing (possibly once weekly or less).

• Activates endogenous insulin receptor signaling pathways.

Citation

• Clinical trial databases (clinicaltrials.gov, PubMed) for emerging data.

• Patent literature (Google Patents, USPTO) for structural and synthetic insights.

• Scientific publications on fatty acid-acylated insulin analogues, albumin binding, and long-acting basal insulins.

• Keywords for literature search include “Insulin 0143-0406,” “long-acting insulin,” “acylated insulin,” “albumin binding insulin analogue,” and “insulin receptor binding.”