Resources on peptide synthesis and drug design, noncanonical amino acids, stable-isotope chemistry and mass-spectrometry analysis.
Curated reading paths
Follow the real development paths of Enlicitide and ICOTYDE from screening hits and structural optimization to oral exposure and clinical translation.
A continuous path from ultra-large libraries, noncanonical amino acids and cyclization to selection trajectories and AI-assisted design.
A practical path from sequence and synthesis-risk assessment to HPLC purity, salt-form and solubility decisions across custom synthesis, purification and quality control.
Use D-amino acids, N-methylation and conformational constraints to balance activity, stability, permeability and manufacturability.
A combined path through internal-standard selection and labeling chemistry, from ¹³C/¹⁵N and deuterium strategies to isotope effects, Delta MS and quantitative applications.
Connect small-molecule quantitation, isotope-labeled standards, TDM and immunoassay comparisons into a clinical-MS method strategy.
Published resources
All categories · 36 articles
Starting from the approval of two oral cyclic peptides, this article analyzes R&D opportunities for cyclic peptide therapeutics in antibody replacement, targeted radiopharmaceuticals, chronic diseases, intracellular protein–protein interactions, and targeted protein degradation.
Compare the targets, discovery technologies, molecular optimization, and oral delivery strategies of the two oral cyclic peptide drugs Icotrokinra and Enlicitide to understand how they are turning the drug space between traditional small molecules and antibodies into an actively developable direction.
From first-in-human exposure to FRONTIER and ICONIC, icotrokinra ultimately demonstrated that an oral cyclic peptide of nearly 1900 Da can translate limited absorption into clinical efficacy for patients and become an FDA-approved drug.
icotrokinra still has difficulty crossing the intestinal epithelium, but its gastrointestinal stability, 200 mg dose, and picomolar-level potency allow even limited absorption to generate effective systemic exposure.
Starting from oral proof-of-concept lead Compound 1a, the team addressed oxidation, solubility, process-safety, and isomer liabilities through a five-module platform and selected Compound 18—MK-0616/Enlicitide.
Peptide 1185 is already stable and highly engineered, so why continue to modify a small number of residues? This article uses real patent SAR to distinguish experimental results from structural interpretation.
The oral development of ICOTYDE first addresses not substantial systemic absorption, but gastrointestinal stability. Peptide 1185 demonstrates how cyclization, terminal capping, and engineered residues such as Pen, 2-Nal, F(4-2ae), and Lys(Ac) can jointly expand the chemical space of natural peptides.
From the established bicyclic platform to tricyclic Compound 35 and property-engineered Compound 44, the program combined potency, stability, PK, and an enabled formulation to demonstrate oral PCSK9 target engagement in primates.