SCPDG Announces our November 12 meeting

Presentation 1 (15 Min)

Application of the Standard Proteasome Recognition Sequence, Leu-Leu-Val-Tyr, as a Prodrug Recognition Motif

Presented by

Robert Anthony Zepeda

Pharmaceutical Sciences (Medicinal Chemistry) under Prof. Darci J. Trader

University of California, Irvine

Abstract: Plants and animals have been used throughout history to treat diseases, ailments, and injuries. It was not until major advances in chemistry were made that they allowed scientists to fully understand why certain plants and animals have medicinal properties. It is no wonder more than half of the chemotherapeutics on the market are derived from natural sources; two popular examples are Monomethyl Auristatin E (MMAE) and Doxorubicin (Dox). MMAE is a derivative of the natural product dolastatin 10 and is widely used in antibody-drug-conjugates as it will inhibit cell division by blocking polymerization of tubulin. Dox is a derivative of its natural product counterpart daunorubicin and performs its cytotoxic effects by inhibiting crucial DNA repair/transcription enzyme topoisomerase 2 while simultaneously interchelating itself into DNA. These highly effective chemotherapies have both been used in the treatment of various diseases using different methodologies of delivery. To achieve higher selectivity with lower off target effects, a new delivery method must be developed. In many disease states, there is an overexpression of a crucial protein complex called the proteasome that is crucial for many disease state progressions. The proteasome is a multicatalyic-multisubunit enzyme that’s primary function is to hydrolyze peptide bonds into smaller fragments to regulate protein homeostasis in the cell. By taking advantage of the abundantly expressed proteasome, a prodrug has been made with a peptide sequence that is known to be hydrolyzed by the proteasome to deliver MMAE and Dox to MM cells in a dose dependent manner. This paper investigates the possibility of a viable proteasome-dependent prodrug technology that can be used for the treatment of diseases that rely heavily on the proteasome.

Presentation 2 (45 Min)

Invisible Risks: Toxicology Strategies for Impurities & Leachables

Presented By

Andrea Rodrigues, PhD, DABTAbbVie

Irvine, California

Abstract: This presentation will provide an overview of the principles guiding the safety evaluation of impurities and leachables in pharmaceutical products. It will address regulatory-imposed limits, key components of a comprehensive risk assessment, and considerations for determining when a qualification toxicology study is warranted. Practical application of these concepts will be illustrated through case studies in ophthalmology and oncology, highlighting the unique challenges associated with different routes of administration, patient populations, and therapeutic contexts. The discussion will emphasize a science- and risk-based approach to evaluating potential patient exposure and supporting appropriate regulatory and development decisions.

Agenda: This is a hybrid event. On-site check-in and networking from 4:00-4:30 PM PT. Zoom login will open at 4:15 PM PT. Presentations and Discussion will be from 4:30-6:00 PM PT. There is no charge for on-site or virtual attendance.

Registration: Please register by 12:00 PM PT, Tuesday, November 10.

Important Notes: You must register to receive an emailed Zoom link for virtual attendance. You will receive the Zoom link after registration closes. The link will be sent to the email used to register. If you need assistance logging in or during the presentation, please text Bobbie at 714 606 5907.