Cambridge Healthtech Institute 제10회

Inflammation Inhibitors
(염증 억제제)

자가면역질환과 염증 관련 경구 치료제의 의약화학

2019년 4월 10일-11일

 

제약 업계에서는 염증 및 자가면역 관련 증상에 대응하는 저분자 기반 약제의 발견, 개발에 주력하고 있습니다. 류마티스 관절염용 최초의 경구 치료제는 저분자 JAK 키나아제 저해제로, 수년 전에 발매되었습니다. 이 항염증약(대부분 저분자 의약품이나 일부 대환식 펩티드 및 구속성 펩티드도 세포내에 침투 가능)은 경구 기반이므로 환자에게 큰 편리성을 제공한다는 점뿐만 아니라 염증 및 자가면역 관련 증상에 영향을 미치는 많은 세포내 분자에 관한 과학적 정보를 단시간에 축적할 수 있다는 점에서도 주목받고 있습니다. 염증 억제제를 테마로 한 이 컨퍼런스 프로그램에서는 면역학 관련 Drug Discovery 표적을 연구하고 있는 화학 및 생물학 연구자가 한자리에 모여 이 분야의 새로운 발견 및 의약화학 연구의 최신 성과에 대해 의견을 교환합니다.


Final Agenda

Wednesday, April 10

12:30 pm Registration Open

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

염증과 자가면역질환용 세포내 키나아제 저해제( 및 각종 저해제)

1:30 Welcome Remarks

Anjani Shah, PhD, Senior Conference Director, Cambridge Healthtech Institute

1:35 Chairperson’s Opening Remarks

Derek Cole, PhD, Director, Medicinal Chemistry, Takeda San Diego

1:40 FEATURED PRESENTATION: Discovery of a Cross-Species Potent and Selective Inhibitor of Receptor-Interacting Protein Kinase (RIPK1) Providing Protection in a Number of Immunological Models

Snahel Patel, PhD, Scientist, Discovery Chemistry, Genentech, Inc.

Regulation of cell death signaling is critical for the maintenance of homeostasis and prevention of disease. Necroptosis, a caspase-independent regulated form of cellular death, is emerging as an important mediator of a number of human pathologies. Activation of necroptotic signaling through TNF signaling or organ injury activates RIPK1 and RIPK3 leading to inflammatory cell death. We present the development of a cross-species potent and selective small molecule inhibitor of RIPK1 to explore the prevention of cell death in a number of disease models of inflammation.

2:10 Considerations in the Generation of Covalent BTK Inhibitors

Noel S. Wilson, MSc, Senior Scientist III, Discovery Chemistry and Technology, AbbVie

Bruton tyrosine kinase (BTK) plays a central role in signaling from the B-cell receptor, which has prompted the development of small-molecule BTK inhibitors for the treatment of autoimmune conditions. The design strategy of irreversible kinase inhibitors, as well as the extensive modeling and crystallographic support which allowed rapid progress of the program into the clinic, will be disclosed. The culmination of these strategies identified ABBV-105, a selective, covalent inhibitor that is efficacious in a preclinical model for RA.

2:40 Discovery of GS-9876: A Selective SYK Inhibitor for the Treatment of Autoimmune Inflammatory Disorder

Peter Blomgren, PhD, Research Scientist II, Medicinal Chemistry, Gilead Sciences, Inc.

3:10 Sponsored Presentation (Opportunity Available)

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 TYK2 Inhibitors

Andrew Fensome, PhD, Associate Research Fellow, Medicines Design, Pfizer

5:00 PTG-100: An Oral Integrin-Specific Peptide Antagonist for Ulcerative Colitis

David Y. Liu, PhD, CSO, Protagonist Therapeutics

5:30 Breakout Discussions

6:15 Close of Day

6:30 Dinner Short Courses*

*Premium or separate registration required.

Thursday, April 11

8:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


8:45 Welcome Remarks from Lead Conference Director

Anjani Shah, PhD, Senior Conference Director, Cambridge Healthtech Institute

8:50 Plenary Keynote Introduction

8:55 Plenary Keynote: New Ways of Targeting K-Ras

Frank McCormick, PhD, Professor, HDF Comprehensive Cancer Center, University of California San Francisco

Efforts to find drugs that bind K-Ras directly have increased recently, enabled by NMR-based fragment screening, di-sulfide tethering, in silico drug design and biophysical methods such as Second Harmonic Generation (SHG). We will report progress on attacking two sites in the K-Ras protein; cysteine-185 (the site of prenylation), and histidine-95, a residue unique to K-Ras, to develop covalent K-Ras inhibitors, as well as compounds identified by SHG and other methods.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

저분자 의약품에 의한 염증 치료의 새로운 표적

10:40 Chairperson’s Remarks

Snahel Patel, PhD, Scientist, Discovery Chemistry, Genentech, Inc.

10:45 Pharmacological Regulation of the Keap1-NRF2 System Unveils Mitochondrial Targeting in Inflammation

Michelangelo Campanella, PhD, PharmD, Professor and Unit Head, Mitochondrial Cell Biology and Pharmacology, Research Group RVC and University College London Consortium for Mitochondrial Research

My talk will report upon Nrf2 inducers as pharmacological tolls in mitochondrial quality control operated by targeted autophagy. It will also dwell on their targeting of mitochondrial pathways which define autoimmunity and inflammation. The presentation will therefore elaborate on the prominent in cell activity of the non-covalent Keap1-Nrf2 protein-protein interaction (PPI) inhibitor PMI, structurally distinct from the covalent Keap1 modifiers (e.g., sulforaphane) and highlight promising ligands targeting mitochondrial pathways involved in the inflammatory response.

11:15 Novel Small Molecule E3 Ligase Activators as Anti-Inflammatory Agents

Kumar Suresh, PhD, Senior Director, R&D Biology, Progenra, Inc.

In this talk, I will present for the first time discovery and characterization of novel E3 ligase activators that suppress TH2 and TH17 differentiation and exhibit robust anti-inflammatory properties. Nedd4-family E3 ligases, including Itch, negatively regulate inflammatory immune responses by suppressing TH2 and TH17 differentiation and cytokine production. Genetic disruption of Itch leads to the development of multi-system immune disorders and lung inflammation.

11:45 Sponsored Presentation (Opportunity Available)

12:00 pm Targeting TRAF6 E3 Ligase Activity with Small Molecules Combats Chronic Inflammation and Autoimmunity

Kamyar Hadian, PhD, Group Leader, Helmholtz Zentrum München

Constitutive NF-κB signaling represents a hallmark of chronic inflammation and autoimmune diseases. The E3 ligase TRAF6 acts as a key regulator bridging innate immunity, pro-inflammatory cytokines, and antigen receptors to the NF-κB pathway. Here, we present an inhibitor of TRAF6-Ubc13 interaction that reduces TRAF6 activity in vitro and in cells. Importantly, this inhibitor ameliorated inflammation and improved disease outcomes of autoimmune psoriasis and rheumatoid arthritis in preclinical mouse models.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Dessert Break in the Exhibit Hall with Poster Awards Announced

Poster Awards Sponsored by Domainex

자연 면역계의 표적화

2:15 Chairperson’s Remarks

Daniel Dairaghi, PhD, Senior Research Advisor, Medicinal Chemistry, Eli Lilly & Co.

2:20 Bacterial Mediated Chemical Transformations of Autoimmune Drug Metabolism

Jason Michael Crawford, PhD, Associate Professor, Departments of Chemistry and Microbial Pathogenesis, Yale University

Photorhabdus asymbiotica causes soft tissue infections of the skin. This bacterium produces the immunomodulator tapinarof during its pathogenic phase. Tapinarof is in phase 3 clinical trials to treat the skin disorders psoriasis and atopic dermatitis. We demonstrate that bacteria can transform tapinarof into other novel potent products that activate the pathways associated with clinical efficacy and kill inflammatory bacteria of the skin.

2:50 Presentation to be Announced

3:20 Targeting ROR and Other Nuclear Hormone Receptors: Chemistry Challenges and Beyond

Scott Thacher, PhD, CEO, Orphagen

This presentation will cover the chemistry challenges we’ve faced targeting nuclear hormone receptor for inflammation and cancer. A sub-theme will be “finding the right indication for druggable nuclear receptors.” I will also discuss our second-in-line program for antagonists to steroidogenic factor-1 (NR5A1).

3:50 Networking Refreshment Break

4:20 Presentation to be Announced

4:50 Targeting Soluble TNF to Eliminate Chronic Inflammation without Immunosuppression

RJ Tesi, MD, CEO/CMO, Inmune Bio

INB03 is a selective inhibitor of soluble TNF that is a potent anti-inflammatory agent that is not immunosuppressive. Current drug development leverages that important biology as part of therapy for cancer, neurodegenerative diseases and NASH. INB03 is significantly different from existing non-selective TNF inhibitors that block both soluble TNF (the BAD TNF) and trans-membrane TNF (the GOOD TNF). This difference makes all of the difference in safety, efficacy and therapeutic opportunity.

5:20 GSNOR Inhibitors for Inflammatory, Auto-Immune, and Oxidative Stress Based Diseases: RA, IBD, and NASH

Matthews O. Bradley, PhD, Chairman, President and Founder, SAJE Pharma, LLC

S-nitrosoglutathione Reductase (GSNOR) regulates nitrosylation signal transduction pathways and is over-expressed in many inflammatory human diseases. We identified, using X-ray crystallography and predictive in vitro assays, inhibitors of GSNOR that are potent, selective, orally bioavailable, and safe. The compounds inhibit oxidants, cytokines, chemokines, and inflammatory cells both in vitro and in vivo. The lead compound, SPL-891.1, is active in models of RA, IBD, and NASH among others.

5:50 Close of Conference

* 주최측 사정에 따라 사전 예고없이 프로그램이 변경될 수 있습니다.