Metabolic Instability of Peptide Therapeutics:

Mechanisms, Analytical Strategies, and Design Solutions for Clinical Success

DATE

February 26, 2026

TIME

8:00 a.m. PST, 11:00 a.m. EST, 16:00 GMT, 17:00 CET - Duration: 60 Minutes

Overview

Metabolic instability is a key challenge in developing peptide therapeutics, and factors like rapid clearance and complex, multi-pathway biotransformation can further limit their effectiveness. Understanding and addressing these hurdles can unlock the full potential of peptide drugs, enabling them to reach challenging biological targets, support rational chemical design, and achieve clinical success. This webinar presents an integrated mechanism–analytics–design perspective to tackle these challenges and accelerate peptide drug discovery.

Dr. Lionel Cheruzel will review common metabolic pathways for peptide therapeutics and evaluate the in vitro systems used to characterize instability. He will discuss chemical modifications—including noncanonical amino acid incorporation, cyclization, lipidation, and conjugation—to enhance metabolic stability and pharmacokinetics. Case studies of clinical-stage molecules such as semaglutide, tirzepatide, and MK-0616 (enlicitide) will demonstrate how rational design supports clinical success.

Dr. Mingshe Zhu will focus on analytical challenges that limit mechanistic understanding of peptide metabolism. He will explain why conventional LC–HRMS workflows often fail to capture the full peptide metabolite landscape and introduce a universal LC–HRMS approach for comprehensive profiling across proteolytic and non-proteolytic pathways. Case studies with clinically relevant peptides (e.g., semaglutide, cyclosporine A, tirzepatide) will show how advanced analytics reveals uncover metabolic soft spots and supports structure–metabolism understanding.

Key Learning Objectives:

In vitro systems and experimental strategies to characterize peptide instability
Medicinal chemistry and conjugation approaches that improve peptide stability and PK
Limitations of conventional LC–HRMS methods for peptide metabolite profiling
How an advanced LC–HRMS workflow enables comprehensive biotransformation and soft-spot analysis

Brought to you by:

Speakers

Lionel Cheruzel, Ph.D.
Senior Principal Scientist, DMPK,
Genentech

Mingshe Zhu, Ph.D.
Scientific Advisor of DMPK,
BioDuro

Registration

Forwarded this event? Clear the form

Email Address*

Salutation

First Name*

Last Name*

Company*

Company Type*

Job Title*

Job Function*

Job Level*

Address 1*

City*

State*

Zip / Post Code*

Country/Territory/Area*

Business Phone*

Are you looking for outsourcing solutions for your projects?*

I would like to subscribe to BioDuro’s emails to receive the latest news and updates.

BioDuro does not share or sell your personal information.

I would like to receive C&EN’s weekly newsletter with the latest in chemistry news

I would like to receive more information on products and services from the American Chemical Society

address2

*By submitting this form, you agree to receive more information on related products and services from the American Chemical Society and its sponsor via email. You understand that you can withdraw your consent at any time. ACS takes your privacy seriously. For more information, please see the ACS Privacy Policy.

View On Demand Webinars