Cambridge Healthtech Instituteの初開催
Degraders & Molecular Glues: Beyond Oncology
分解剤・モレキュラーグルー：オンコロジーを超えて
Designing and Optimizing PROTACs and Glue Modalities for Diverse Therapeutic Indications
多様な治療適応に対するPROTAC・グルーモダリティの設計と最適化
2025年4月14日
タンパク質分解剤・モレキュラーグルー（分子糊）は、タンパク質間の相互作用を破壊し、ユビキチン・プロテアソーム系、リソソーム、オートファジー系を乗っ取って、標的タンパク質の分解を行うために開発されています。PROTAC（タンパク質分解誘導キメラ分子）のようなヘテロ二官能性の分解剤やモレキュラーグルーのような一価の分解剤の多くは、がんを標的とするために使用されていますが、オンコロジー以外の適応症にも逆風が吹いています。初開催となる「分解剤・モレキュラーグルー：オンコロジーを超えて」シンポジウムは2部構成の会議で、新たな治療アプローチとして、標的タンパク質分解と近接誘導の利用が拡大していることを強調します。
4月14日（月）
12:00 pmPre-Conference Symposium Registration
EXPLORING NEW DEGRADATION PATHWAYS & MODALITIES
新しい分解経路とモダリティを探究
FEATURED PRESENTATION: Destruction with High Specificity: Mechanisms of Substrate Selection and Processing by the 26S Proteasome and p97/Cdc48
Andreas Martin, PhD, Professor and HHMI Investigator, Molecular & Cell Biology, University of California Berkeley
Our biochemical, single-molecule, and cryo-EM structural studies provide important mechanistic insights into the processing of ubiquitinated substrates by the 26S proteasome and the p97/Cdc48 protein unfoldase. We also
recently characterized a novel mode of ubiquitin-independent, NUB1-cofactor mediated degradation by the human proteasome, whereby the ubiquitin-like modifier FAT10 functions in substrate delivery and engagement by the
proteasomal ATPase motor, offering new opportunities for targeted protein degradation independent of ubiquitin or p97.
2:15 pmPresentation to be Announced
2:45 pmSponsored Presentation (Opportunity Available)
3:15 pmNetworking Refreshment Break
Molecular Glue, Mitochondrial Biogenesis, Neurodegeneration, and Aging
Tauseef Butt, PhD, President & CEO, Progenra, Inc.
Misfolded proteins and protein aggregates, such as tau and a synuclein, damage mitochondria leading to cell death. ATP is in high demand by ubiquitin proteasome system to keep the house clean. Progenra has discovered
a potent molecular glue that activates Parkin (E3 ligase)/PINK1 (kinase) signaling pathway. Phosphorylation of ubiquitin and parkin E3 ligase by PINK1 orchestrates mitophagy as well as initiating mitochondrial gene
transcription and translation (mitobiogenesis). Healthy mitochondrial function plays a critical role in protection against Alzheimer’s and Parkinson’s diseases and aging. Phospho-ubiquitin levels in blood act as a biomarker
for healthy aging. Mechanisms of the glue will be discussed.
Targeting 14-3-3/CRAF Complexes with Molecular Glues: Applications in Oncology and RASopathies
Markella Konstantinidou, PhD, Staff Scientist, Laboratory of Dr. Michelle Arkin, Department of Pharmaceutical Chemistry, University of California, San Francisco
The hub protein 14-3-3 plays a pivotal role in controlling CRAF function in the MAPK pathway. 14-3-3 binds to pS259, maintaining CRAF in an inactive state, thus preventing downstream signaling. Mutations in the residues
surrounding the pS259 site occur in developmental disorders termed “RASopathies.” We have developed molecular glues targeting the 14-3-3/CRAF wild-type autoinhibited complex with applications in RAS-driven cancers,
as well as molecular glues targeting the mutated RASopathy complexes.
5:15 pmClose of Symposium
5:30 pmDinner Short Course Registration
6:00 pmDinner Short Course*
SC1: Protein Degraders: A Beyond Rule of Five Space and in vitro ADME Perspective
*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。
2025年 4月 14日
2025年 4月 15 - 16日
2025年 4月 16 - 17日
