Physicochemical Property Analysis
(물리 화학적 성질 분석)
물리적 성질의 최적화에 의한 Drug Discovery 프로세스의 개선
4월 18-19일

생체내에서의 흡수와 분포에 다양한 영향을 미치는 등 화합물의 물리적인 성질(물성)의 최적화는 Drug Discovery 프로세스의 기본입니다. 화합물의 물성을 조사함으로써 생체내에서의 화합물 수송 프로세스에 관한 정보를 얻을 수 있으며, 물성을 파악함으로써 과제를 위한 최적의 화합물을 선별할 수 있습니다. 또한 개발 단계로 나아가기 전의 설계 단계에서 화합물 분석을 적정하게 진행함으로써 경비와 시간을 절약할 수 있습니다. Drug Discovery 프로세스에서는 개발된 의약품의 용해도에 화합물의 소수성이 미치는 영향과 화합물의 투입량과 수송 메커니즘에 의한 흡수와의 상호작용이라는 문제를 고려하는 것이 중요하기 때문입니다. 예측 모델을 이용하는 것도 중요하나, 새로운 화합물이 가지고 있는 실제 물리화학적 성질을 제대로 고려하지 않으면 실제와는 다른 데이터를 기반으로 한 분석이 되어버릴 가능성이 있습니다. 이 컨퍼런스에서는 엄선된 효과가 높은 화합물을 개발하고, 화합물의 물리화학적 성질을 조기에 분석하여 생물학적 데이터를 정확히 이해하기 위해 필요한 요소를 중심으로 논의가 진행됩니다.

현재 연사를 모집하고 있습니다.

새로운 접근법을 고안하신 분, 공표가능한 새로운 데이터를 가지고 계신 분, 사례 연구와 교훈을 다른 연구자에게 전하고 싶으신 분들의 응모를 기다리고 있습니다. 최신 연구 성과와 전문 지식을 이번 컨퍼런스에서 공개하고 싶으신 약학 분야의 연구자와 전문 기술자 여러분의 많은 참여 바랍니다. 응모시 연락처를 알려주시기 바랍니다.

강연 시간이 제한되어 있으므로, 제약회사 및 바이오테크놀러지 관련 기업, 감독기관, 연구센터 등에 소속된 분들을 우선으로 합니다. CHI의 방침에 입각하여 생물의약품 연구자를 대상으로 제품 및 서비스를 제공하고 있는 벤더 및 컨설팅회사 여러분을 위해 한정된 수이나, 각종 기업 스폰서 프로그램을 기반으로 한 프레젠테이션 코너도 마련했습니다.

첫째날 | 둘째날

4월 18일, 수요일

12:30 pm Registration

1:30 Chairperson’s Opening Remarks

THE PATH AHEAD

1:40 Getting Physical in Drug Discovery; Where Next for Property Profiling and Predictive Methods?

Robert J. Young, Ph.D., GlaxoSmithKline

A growing body of evidence indicates that much of the attrition in drug discovery can be attributed to the sub-optimal physical properties of experimental molecules, especially in pre-clinical activities. Molecules that are overly lipophilic and/or highly aromatic have been shown to posses greatly increased risk in studies to assess developability and promiscuity profiles; with impact over and above the inherent correlation between logP and #Ar rings. This led to the so-called property forecast indices, (PFI = log P or log DpH7.4 + #Ar), simplistic yet powerful predictors of risk; these are enhanced by the utilisation of improved lipophilicity measures and estimates based on chromatographic methods. Data illustrating these principles will be discussed, posing questions for future predictive methods. Successful molecules can be further discriminated when PFI is taken together with ligand efficiency measures, pointing to a useful indicator of likely success in drug discovery.

2:55 Getting Physical in Drug Discovery: A Suite of Physicochemical Methods to Enable Successful Drug Discovery

Alan P. Hill, Ph.D., Team Leder, PhysChem, Department of Analytical Chemistry, GlaxoSmithKline, Stevenage UK

Physicochemical measurements are key enablers for successful medicinal chemistry. However to maximise the likelihood of a success, it is essential that assays offered provide data that is appropriate to the stage of the project and additionally have sufficient capacity to meet demands. The presentation will provide an overview of a cohesive approach to physicochemical measurement (as applied within GSK) that effectively guides medicinal chemistry projects to produce robust candidate molecules with optimal physicochemical properties.

3:10 Modulating Physicochemical Properties to Improve ADME Outcomes

Jan Wahlstrom, Ph.D., Principal Scientist, Amgen

Alterations of physicochemical properties such as molecular weight, log d, polar surface area or pKa may influence the absorption, distribution, metabolism or excretion (ADME) of a chemical series in a chemotype-dependent manner. Application of mechanistic approaches to solving ADME issues provides insight as to why a change in properties causes a desired outcome in some cases, while leading to poorer outcomes in others. This seminar will focus on case studies outlining common ADME issues faced during the drug discovery process and the approaches used to resolve them.

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

4:20 Practical Concepts in Fragment-Based Drug Ddiscovery

Marcel Verdonk, Ph.D., Director, Computational Chemistry and Informatics, Astex Therapeutics, Inc.

INTERPRETING DATA

4:50 The Intricacies of Interpreting Pharmaceutical Data

Terry Stouch, Ph.D., President, R&D, Science for Solutions, LLC

Pharmaceutical research data that is extremely valuable within context could be worthless outside of that context or when lumped with other data. We will discuss these issues supported by many practical examples from several pharmaceutical companies, commercial and open source databases, and the literature. Diverse types of pharmaceutical data will be discussed including physicochemical properties such as solubility, logP, logD, Caco-2, and pKa. The vital meta data, its importance in the proper use of the data, the mistakes and problems that arise from ignoring it, and the reasons it is often ignored, will be outlined. Recommendations that will ameliorate these problems and enhance data use and value will be offered for better data capture and data basing and for holistic data presentation that will aid interpretation.

5:20 Interactive Breakout Discussions

In this interactive session, several topics will be offered for discussions and delegates are invited to choose a breakout topic of interest and join the moderated discussion at hand. In this informal setting, participants are encouraged to share examples from their work, vet ideas with peers and be part of a group problem-solving endeavor. We emphasize that this discussion is an informal exchange amongst scientists and is not meant to be, in any way, a product discussion.

Topic 1: Challenges of Thermodynamic Analysis

Moderator: Ernesto Freire, Ph.D., Henry Walters Professor, Johns Hopkins University

Topic 2: Hydrophobicity in Drug Discovery: Measurement or Calculation: Which Moves Drug Discovery Forward?

Moderator: Alan P. Hill, Ph.D., Team Leder, PhysChem, Department of Analytical Chemistry, GlaxoSmithKline, Stevenage UK

• When is hydrophobicity important?
• Is calculation good enough?
• logP or LogD?

6:30 End of Day