Cambridge Healthtech Instituteの第2回年次会議
Covalent Modifications & Induced Proximity
（共有結合修飾・近接の誘導）
革新的な化学と戦略が共有結合による創薬を促進
2023年4月10日 | 1:00PM-5:15PM（米国太平洋標準時）
近接は、特定の生物学的相互作用や、ユビキチン化、リン酸化、メチル化、アセチル化などの翻訳後修飾において重要です。化学的に誘導された近接が新たな関心領域で、共有結合化学を利用して近接を誘導し、タンパク質分解誘導、タンパク質安定化、タンパク質フォールディング、クロマチン調節などの生物学的プロセスをトリガーします。「共有結合修飾・近接の誘導」に関するこのシンポジウムでは、創薬化学、ケミカルバイオロジー（化学生物学）、プロテオミクスのグループから学術研究者や業界の科学者が集まり、メカニズム研究や治療的介入に対する近接の誘導に活用できる革新的な化学や技術について議論します。
4月10日（月）
Pre-Conference Symposium Registration Open12:00 pm
Welcome Remarks1:00 pm
In-Cell Proteome-Wide Covalent Ligand Discovery
Brent Martin, PhD, Vice President, Chemical Biology, Scorpion Therapeutics
Many proteins exist in unique conformations or form interactions present only within their native cellular environment. We have developed proteome-wide cysteine profiling methods and identified covalent fragments with high occupancy for therapeutically relevant targets. Key insights, examples, and lessons learned will be presented.
FEATURED PRESENTATION: A New Class of Therapeutics Based on Chemically-Induced Proximity
Gerald Crabtree, MD, David Korn Professor of Experimental Pathology & Developmental Biology, Stanford University
With Stuart Schreiber’s group we developed chemical inducers of proximity to probe the role of this fundamental physical process in biologic mechanisms such as signal transduction, transcription, epigenetics as well as protein location, regulation and stability. These early studies used genetically tagged proteins or nonspecific small molecules, but pointed the way to approaches using no genetic tags that capitalize on underlying biologic specificity. I will discuss some of the later in more detail.
Targeted Covalent Inhibitor Assay Strategies: ADME Perspective
Upendra Dahal, PhD, Senior Principal Scientist, Pharmacokinetics and Drug Metabolism, Amgen, Inc.
Targeted covalent inhibitor (TCI) approaches are an emerging small molecule drug modality where a covalent bond between a drug and a target protein forms by design. TCI drugs are regaining momentum as an attractive small molecule drug modality that can be applied to protein targets which have been previously considered undruggable. This presentation will discuss the challenges and strategies for the development of TCI drugs from absorption, distribution, metabolism, and excretion (ADME) perspective. Unique assays are required to support development of TCIs and will be presented with examples.
Sponsored Presentation (Opportunity Available)2:45 pm
Networking Refreshment Break3:00 pm
A Photocatalytic Toolbox for Mapping Novel Protein Pairings at the Cell Surface
Rob Oslund, PhD, Vice President, Platform Technologies, InduPro, Inc.
Inherent proximity of cell surface protein environments not only influences how proteins function but also informs our ability to effectively target/modulate cell surfaces for therapeutic benefit. This talk will describe the development of a novel light-mediated catalytic proximity labeling toolbox for identifying proximal protein environments for clinically-relevant surface proteins as well as downstream applications of the technology.
FEATURED PRESENTATION: Reimagining Druggability Using Chemoproteomic Platforms
Daniel Nomura, PhD, Professor of Chemistry, Molecular and Cell Biology, Nutritional Sciences and Toxicology, University of California, Berkeley
We currently have three major research directions. One is developing and applying chemoproteomics-enabled covalent ligand discovery approaches to rapidly discover small-molecule therapeutic leads that target unique and novel ligandable hotspots for undruggable protein targets and pathways. Second focus is on using chemoproteomic platforms to expand the scope of targeted protein degradation technologies. Our third area focuses on using chemoproteomics-enabled covalent ligand discovery platforms to develop new induced proximity-based therapeutic modalities. This talk will focus on using covalent chemoproteomic strategies for drugging undruggable oncogenic transcription factors and also developing new induced proximity-based therapeutic modalities beyond degradation.
In-Person Group Discussion4:30 pm
Close of Symposium5:15 pm
Dinner Short Course Registration5:15 pm
Dinner Short Courses*6:00 pm
*Premium Pricing or separate registration required. See Short Courses page for details.
* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。
