The Mastering Medicinal Chemistry conference is now in its fifteenth year and continues to remain one of the most popular events of its kind. Each year we strive to bring you the hottest topics in medicinal chemistry from leaders in the
pharmaceutical, biotech and academic spaces. We showcase the biggest opportunities for small molecules through cutting-edge case studies, panel discussions, poster presentations and breakout discussions. Mastering Medicinal Chemistry – Part 2 will feature case studies and new research in kinases, covalent inhibitors, protein-protein interactions, epigenetics and future role of medicinal chemistry.
This conference follows Mastering Medicinal Chemistry – Part 1 being held from June 13-14, 2017. Together, these two events will provide three full days of programming on the hottest trends and targets being pursued in small molecule
drug discovery. We cordially invite you to present a poster, or to attend to learn from and network with the leading experts from around the globe.
Final Agenda
Wednesday, June 14
11:00 am Registration
12:00 pm Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:30 Session Break
1:00 Coffee and Dessert in the Exhibit Hall with Poster Viewing
1:30 PLENARY KEYNOTE SESSION
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Chairperson’s Opening Remarks
Henning Stockmann, Ph.D., Senior Scientist, Chemical Biology, AbbVie Inc.
4:25 FEATURED PRESENTATION: Ligand-Induced Kinase Degradation
Lyn H. Jones, Vice President, Chemical Biology, Jnana Therapeutics
We have discovered a pan-JAK ATP-competitive inhibitor that causes selective degradation of JAK2 and JAK3 in human primary cells at low concentrations. This work suggests that ligand-induced kinase degradation warrants further investigation as it may
hold significant promise as a useful therapeutic modality.
4:55 VX-787 (JNJ872): Phenotypic Screen & Target Identification for a First-in-Class, Orally Bioavailable Inhibitor of Influenza PB2
Michael P. Clark, Director, Department of Chemistry, Vertex Pharmaceuticals Inc.
A phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. This class of inhibitors was optimized using
a bDNA viral replication assay to afford VX-787 (JNJ872). VX-787 represents a first-in-class, orally bioavailable, novel compound that offers unparalleled potential for the treatment of both pandemic and seasonal influenza.
5:25 Integrating Data and Design to Target High Quality Compounds
Tamsin Mansley, Ph.D., Head of North American Operations, Optibrium
A high-quality drug must exhibit a balance of many properties, including potency, ADME and safety. In this presentation, we’ll discuss Multi-parameter Optimization (MPO) methods that guide the selection and design of compounds with the highest
chance of success, while minimizing opportunities missed by inappropriately rejecting compounds. This will be demonstrated with an application that seamlessly integrates data visualisation, MPO and design, in the context of an example project.
5:55 New Chemical Biology Technologies for Target Identification and High-Throughput Screening: Chemical Glycobiology and Beyond
Henning Stockmann, Ph.D., Senior Scientist, Chemical Biology,
AbbVie Inc.
Improved strategies for reliable drug target identification and target engagement studies are urgently needed, whereby cell-surface receptors present particular challenges. We have developed new chemical biology approaches to link probes and reporters
to cell-surface receptors and cytosolic proteins in live cells. Our sugar-based cell-surface engineering methods not only enable receptor visualization, isolation, and proteomics-based characterization, but also facilitate target engagement
studies and high-throughput ligand binding assays in intact cells.
6:25 Close of Day
6:30 Dinner Short Course Registration
Thursday, June 15
7:15 am Registration Open and Morning Coffee
7:30 Interactive Breakout Discussion Groups with Continental Breakfast
This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas
and active networking. Continental breakfast is available for all participants.
Topic: Chemical Biology
Moderator: Henning Stockmann, Ph.D., Senior Scientist, Chemical Biology, AbbVie Inc.
- New approaches to target identification
- In vitro and in vivo measurement of target engagement
- Emerging topics in chemical biology
Topic: Separation Challenges in Drug Design
Moderator: Carol Moraff, Scientific Associate I, Novartis Institutes for BioMedical Research
- What are the most difficult types of compounds to purify (& potential solutions)?
- New analytical technology – what has been useful, what problems still need to be solved?
- Next steps – what changes in the types of molecules being produced will require adjustments to separation techniques and abilities?
8:35 Chairperson’s Remarks
Lieven Meerpoel, Ph.D., Senior Director, Janssen Lead Discovery, Janssen R&D
8:45 KEYNOTE PRESENTATION: Exploring the Pluridimensionality of G Protein-Coupled Receptor Signaling Efficacy; Potential Impacts for Drug Discovery
Michel Bouvier, Ph.D., Professor/General Director, Biochemistry and Molecular
Medicine/Institute for Research in Immunology and Cancer, Université de Montréal -
It is now clear that G protein-coupled receptors can engage signaling pathways in a ligand-specific manner. Using BRET-based biosensors detecting the activity of multiple signaling pathways in living cells we characterized compounds based on multi-parametric
analysis of their efficacy. Such pluridimensional description of compounds allows correlating signaling signatures to specific biological outcomes. Combined with structural analyses of the receptors, it also provides insights into the molecular
basis of functional selectivity paving the way for the development of rationally designed biased ligands.
9:15 Discovery of Novel Macrocyclic Inhibitors of Elongation Factor-2 Kinase as Anti-Cancer Agents
Lieven Meerpoel, Ph.D., Senior Director, Janssen Lead Discovery, Janssen
R&D
Macroclyclic EF2k inhibitors were designed that inhibit phosphorylation of EF2 at nM concentrations in metabolically stressed MCF10A cells. Minor modifications on the macroclyclic linker, including introduction of chirality, had major effects
on EF2K activity, kinase selectivity, ADME and in vivo PK properties. Genetic and proteomic enabled deconvolution of potent EF2K versus VPS34 inhibitors. Tumor cell line profiling did not reveal intrinsic
sensitivity to EF2K inhibition. Vps34 inhibition abrogates autophagy flux, and is anti-proliferative in a subset of tumor cell lines.
9:45 Selected Poster Presentation: Applying Nature-Inspired 3D-Fragments Towards the Discovery of nM Inhibitors of Cyclophilin D
Eric A. Jamois, Ph.D., Head of US Business Operations, Edelris SAS
Cyclophilins are folding helper enzymes of the Peptidyl Proline Isomerases (PPI) superfamily with a strong reputation as extremely challenging targets. Our research focused on the identification of non-immunosuppressive Cyclophilin D (CypD) inhibitors
and their potential implication in mitochondrial function. We will discuss the results obtained in a collaborative FBDD program with Merck Serono, culminating in the identification of a highly potent (nM) inhibitor of Cyclophilin D.
10:15 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Investigating Small Molecules to Inhibit GLK/MAP4K3 and Prevent PKCp Phosphorylation Potential Therapy to Modulate T Cell Dependent Effector Functions
Tricia May-Dracka, Ph.D., Scientist II, Chemistry and Molecular
Therapeutics, Biogen
Germinal center kinase-like kinase (GLK) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-p (PKCp in T cells. Controlling T helper cell
responses would be valuable for treatment for autoimmune diseases. I will disclose for the first time our efforts to identify a potent and selective GLK inhibitor, aided by the first crystal structure of GLK.
11:30 Phenotypes of a Novel Series of 3-Phosphoglycerate Dehydrogenase Inhibitors
Nello Mainolfi, Ph.D., Senior Director, Head of Drug Discovery, Raze
Therapeutics
PHGDH (3-phosphoglycerate dehydrogenase) is the first enzyme branching from glycolysis into the serine synthetic pathway. Increases in PHGDH expression (mRNA and protein levels) have been observed in nearly 70% of estrogen receptor-negative
breast cancers. We have been able to successfully identify first in class small molecule inhibitors with nanomolar cellular potency, high degree of selectivity and oral bioavailability
12:00 pm Covalent Inhibitors for Glycan-Modifying Enzymes
Gerd Wagner, Ph.D., Reader in Medicinal Chemistry, Department of Chemistry,
King’s College London
Inhibitors and chemical probes for glycosidases and glycosyltransferases enzymes are of great interest for chemical biology and drug discovery in areas such as infection, inflammation and cancer. However, the development of such inhibitors
with drug-like properties remains a formidable challenge, in particular for glycosyltransferases. The presentation will demonstrate how principles of covalent inhibitor discovery can be harnessed to address this challenge, focusing in
particular on bacterial enzymes.
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:00 Session Break
1:30 Chairperson’s Remarks
Salvador Ventura, Ph.D., Professor/Group Leader, Deptartment of Biochemistry and Molecular Biology, Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona
1:35 Development of Protein-Protein Interaction Inhibitors and Use of Biophysical Screening
Kevin Lumb, Ph.D., Global Head of Screening, Discovery Sciences, The Janssen Pharmaceutical
Companies of Johnson & Johnson
2:05 Interdiction at a Protein-Protein Interface: Structure-Based Design of Mcl-1 Inhibitors
Sean P. Brown, Ph.D., Principal Scientist, Medicinal Chemistry, Amgen
Although compelling, targeting disruption of Mcl-1’s protein–protein interaction to induce tumor cell death was previously thought to be “un-druggable” due to the high affinities of Mcl-1 to the pro-apoptotic Bcl-2
proteins and lack of a small molecule binding pocket. This presentation will describe the convergence of structural information and small molecule conformational analysis applied to the optimization of small molecule high-throughput screening
hit to this now “druggable” target.
2:35 Refreshment Break in the Exhibit Hall (Last Chance for Poster Viewing)
3:20 Targeted Protein Degradation
Andrew J. Phillips, Ph.D., President and CSO, C4 Therapeutics
Emerging capabilities and concepts in targeted protein degradation will be described with a special focus on (i) the discovery and optimization of potent degraders of chromatin reader proteins, and (ii) the degradation of transmembrane proteins.
3:50 Repositioning Tolcapone as a Potent Inhibitor of Transthyretin Amyloidogenesis and Associated Cellular Toxicity
Salvador Ventura, Ph.D., Professor/Group Leader, Department
of Biochemistry and Molecular Biology, Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona
Transthyretin (TTR) is implicated in fatal systemic amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson’s disease, as a very potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human
plasma, stabilizes the native tetramer in humans and inhibits TTR cytotoxicity. This converts tolcapone in a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for
which no small molecule therapy exists.
4:20 PANEL DISCUSSION: Role of Outsourcing and Industry-Academia Collaborations in Shaping the Future of Drug Discovery
Moderator:
Salvador Ventura, Ph.D., Professor/Group Leader, Department of Biochemistry and Molecular Biology, Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona
Panelist:
Kevin Lumb, Ph.D., Global Head of Screening, Discovery Sciences, The Janssen Pharmaceutical Companies of Johnson & Johnson
Sean P. Brown, Ph.D., Principal Scientist, Medicinal Chemistry, Amgen Andrew J. Phillips, Ph.D., President and CSO, C4 Therapeutics
5:00 Symposia Registration