Cambridge Healthtech Institute’s 15th Annual Mastering Medicinal Chemistry conference will bring together senior level medicinal chemists in pharmaceutical, biotech, and academia. Through new case studies, informative
panel discussions, high-level poster presentations, and interactive breakout discussions, top scientists will share new insights into small molecules. This event will cover key topics currently facing medicinal chemists, including emerging targets,
receptor kinetics and high-throughput experimentation. The Mastering Medicinal Chemistry conference- Part 1 will focus on the recent medicinal chemistry advancements in the field of immuno-oncology.
Final Agenda
Tuesday, June 19
7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)
8:15 Chairperson’s Opening Remarks
Lijun Sun, PhD, Director, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School
8:20 Challenges in Phenotypic, Target Agnostic Drug Discovery: Lessons Learned from a Cell-Based Screen Designed to Identify Small Molecules that Decrease C-MYC in Cancer Cells
Jesus Medina, PhD, Manager, Medicinal Chemistry, GlaxoSmithKline
One of the key challenges in cell-based phenotypic drug discovery efforts is the early assessment of the validity and viability of hits obtained from the screen. Using our c-MYC cellular screen as an example, we describe a strategy to determine whether
the MOA of the hits has in vivo translatability. The details of our screening strategy/triage campaign, molecular target identification efforts, results from in vivo studies,
and the lessons learned along the way will be discussed.
8:50 Rational Design of AKR1C3 Inhibitors as Chemotherapeutic Potentiators
Paul Trippier, PhD, Professor, Department of Pharmaceutical Sciences, Texas Tech University
Health Sciences Center
Aldo–keto reductase 1C3 (AKR1C3) catalyzes the downstream conversion of androgen precursors to the potent androgen receptor ligands testosterone and 5α-dihydrotestosterone, and conversion of PGD2 to 11β-PGF2α and PGF2α
prostanoids and hence acts as an important regulator of myeloid cell proliferation and differentiation. The enzyme is highly upregulated in prostate cancer and a number of leukemias. We have designed potent and highly selective inhibitors that
act to potentiate clinical chemotherapeutics >200-fold. Such action results in reduced dosing, reduced toxic side effects and completely counters AKR1C3-mediated drug resistance. Our inhibitors provide a strategy for treating vulnerable patients
diagnosed with these and other neoplasms in combination with existing chemotherapeutics
9:20 Discovery and Preclinical Characterization of GSK532, a Highly Efficacious STING Agonist for Immuno-Oncology
Yiqian Lian, PhD, Program Team Leader, Immuno-Oncology & Combinations DPU, GlaxoSmithKline
The cGAS-STING pathway plays a crucial role in body’s spontaneous sensing of tumor by the immune system. Unlike checkpoint inhibitors that unleash the body's tumor immune response, STING agonists prime tumor immunity by initiating tumor antigen
presentation and tumor specific T-cell response. Herein, we report the discovery of highly efficacious novel STING agonist GSK532 for application in immuno-oncology.
9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
10:35 Selective Inhibitors of CLK And DYRK Kinases and Their Anticancer Activity
Lijun Sun, PhD, Director, Center for Drug Discovery and Translational Research, Beth Israel Deaconess
Medical Center, Harvard Medical School
CDC2-like kinase (CLK) and dual specific tyrosine phosphorylation-regulated kinase (DYRK) control the mRNA splicing events via priming phosphorylation of key SF members of the spliceosome. CLK and DYRK are aberrantly activated in a number of cancers
and are attractive targets for developing anticancer therapy. We describe our SAR results of a class of novel water-soluble benzimidazoles as selective CLK/DYRK inhibitors. In vitro activity in the NCI60 panel
screen of the advanced lead candidates, as well as in vivo efficacy in established prostate cancer tumor models, will be presented.
11:05 Modulation of Innate B1 Lymphocyte Immune Response in Cancer
Nikolai Tupitsyn, PhD, Professor, Cancer Immunology, Lab, Blokhin Cancer Research Center
B1 natural pentameric immunoglobulins can destroy cancer cells. This is selective process usually being directed against tumor associated glycans not expressed by normal cells. Monoclonal antibodies to tumor associated glycan proved their efficacy
in gastric cancer. Is there any possibility to use immunoadjuvants to elevate natural B1 immunity to effective level?
11:35 Sponsored Presentation (Opportunity Available)
12:05 pm Session Break
12:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:40 Session Break
1:15 Chairperson’s Remarks
Atli Thorarensen, PhD, Research Fellow, BioTc Medicinal Chemistry, Pfizer
1:20 Discovery and Optimization of a Novel Series of Highly Selective JAK1 Kinase Inhibitors
Neil Grimster, Senior Scientist, Oncology Chemistry, AstraZeneca
Janus kinases (JAKs) have been demonstrated to be critical in cytokine signaling, and have thus been implicated in both cancer and inflammatory diseases. The development of small molecule inhibitors that are selective for a specific family member
would represent highly desirable tools for deconvoluting the intricacies of JAK family biology. Here we present the discovery of a potent and orally bioavailable JAK1 inhibitor, which possess ~1000 fold selectivity over the other highly homologous
JAK family members, and good selectivity over kinases in general.
1:50 Optimization of Kinact Delivers a First in Class Specific Covalent JAK3 inhibitor PF-06651600
Atli Thorarensen, PhD, Research Fellow, BioTc Medicinal Chemistry, Pfizer
Janus kinases (JAKs) have been demonstrated to be critical in cytokine signaling, and have thus been implicated in both cancer and inflammatory diseases. The development of small molecule inhibitors that are selective for a specific family member
would represent highly desirable tools for deconvoluting the intricacies of JAK family biology. Here we present the discovery of a potent and orally bioavailable JAK1 inhibitor, which possess ~1000 fold selectivity over the other highly homologous
JAK family members, and good selectivity over kinases in general.
2:20 Aspartyl(Asparaginyl)-Beta-Hydroxylase Inhibitors for the Treatment of Cancer
Mark Olsen, PhD, Associate Professor, Medicinal Chemistry, Pharmaceutical Sciences, Arizona College of Pharmacy
2:50 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)
3:30 A Kinase Inhibitor for a Chronic Indication: A Case Study in Balancing Selectivity and Safety to Advance Potent, Selective and Orally Bioavailable MAP4K4 Leads to Preclinical Toxicity Studies
Samit Bhattacharya, PhD, Senior Principal Scientist, World Wide Medicinal Chemistry, Pfizer
This presentation will describe the identification of an aminopyridine lead series from virtual screening and evolution of multiple aminopyridine leads that led to discovery of advanced potent, selective and orally bioavailable MAP4K4 inhibitors.
Given the concerns of chronic safety for a kinase inhibitor in a non-oncology indication, this presentation will discuss strategies that were employed to advance two chemotypes (PF-06279789 and PF-06745013) with excellent kinase selectivity but
orthogonal profiles to assess safety of the mechanism.
4:00 Chemogenomic-driven Hit Identification to Deliver Novel dF508 CFTR Corrector Leads
John Mathias, PhD, Senior Director, Head of Inflammation & Immunology Design, Pfizer
4:30 Identification of Low Clearance Indole Acid AMPK Activators for the Treatment of Diabetic Nephropathy
David Ebner, PhD, Senior Scientist, Pfizer Research Labs
5:00 Find Your Table and Meet Your Moderator
5:05 Interactive Breakout Discussion Groups
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.
Developing Anticancer Therapies with Dual Specific Kinases
Lijun Sun, PhD, Director, Center for Drug Discovery and Translational Research,
Beth Israel Deaconess Medical Center, Harvard Medical School
- Dual specific kinases and their benefits in treating cancers
- Other therapeutic areas of interest?
- Potential uses of the DYRK
Safety Considerations of Kinase Inhibitors
Samit Bhattacharya, PhD, Senior Principal Scientist, World Wide Medicinal
- Chronic safety concerns for kinase inhibitors for you in non-oncology indications
- Advancing chemotypes
- Using orthogonal profiles to assess safety
5:45 Reception in the Exhibit Hall with Poster Viewing (America Ballroom)
7:00 Close of Day
Wednesday, June 20
7:45 am Registration Open (America Foyer) and Morning Coffee (Foyer)
8:25 Chairperson’s Remarks
Jesus Medina, PhD, Manager, Medicinal Chemistry, GlaxoSmithKline
8:30 Kinetic and Thermodynamic Profiling in Drug Discovery: A Case Study with EED Hit-to-Lead Program
Ying Wang, PhD, Principal Scientist, Department of Chemistry & Technology, AbbVie
Our analysis revealed for the first time that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED amino pyrrolidine compounds were found to be mainly enthalpy driven with improved
enthalpic contributions as the program progressed. We will also present our perspectives on where we are at on harnessing the power of thermodynamic and kinetic profiling in drug discovery.
RORC2 Inverse Agonists: Finding Lipophilic efficiency in a Hydrophobic Pocket
Mark Schnute, PhD, Associate Research Fellow, Medicine Design, Pfizer R&D
Small molecule, inverse agonists of the nuclear hormone receptor RORC2 are potential therapies for several autoimmune diseases through their ability to inhibit pro-inflammatory cytokine production. This presentation will describe how we have used
the key design strategies of lipophilic efficiency optimization and understanding the interplay of structure, pharmacology and target residence time to advance a high-throughput screening hit into a highly potent, selective and orally bioavailable
compound.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
10:45 PANEL DISCUSSION: Medicinal Chemistry in the Field on Oncology and Immuno-Oncology
Jesus Medina, PhD, Manager, Medicinal Chemistry, GlaxoSmithKline
Panelists:
Jesus Medina, PhD, Manager, Medicinal Chemistry, GlaxoSmithKline
Atli Thorarensen, PhD, Research Fellow, BioTc Medicinal Chemistry, Pfizer
Samit Bhattacharya, PhD, Senior Principal Scientist, World Wide Medicinal Chemistry, Pfizer
11:45 Session Break
11:50 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
1:00 PLENARY KEYNOTE SESSION
Essex South
Partnering for Sustainable Funding
The panel is designed to discuss partnering between various stake holders such as drug discovery startups, VC firms, large pharmaceutical companies and academic labs in order to advance new target discovery and preclinical research. VC companies,
and pharma search & evaluation departments will be represented on the panel.
Jens Eckstein, PhD, President, SR One
Barbara K. Sosnowski, PhD, Vice President and Global Head, External R&D Innovation, Pharmatherapeutics and WRD External Partnerships, Pfizer, Inc.
Kevin Bitterman, PhD, Partner, Atlas Venture
Vivian Berlin, PhD, Director of Business Development, Life Sciences, Office of Technology Development, Harvard University
Ben Thorner, Senior Vice President and Head, MRL Business Development & Licensing, Merck
Plenary Technology Panel
Advancing Innovation in Drug Discovery and Translational Research
This year’s Plenary Technology Panel features a group of technical experts from life science technology and service companies, who share their perspectives on various trends and tools that will likely change the way in which we traditionally
approach preclinical drug discovery and development. Attendees will have an opportunity to ask questions and understand the impact of recent technical advances.
Moderator: Leigh Zawel, PhD, Managing Director, MPM Capital
Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com
Stefan Braam, PhD, Technical Director, Ncardia
Mark Paris, PhD, Director, Translational Applications, Mitra Biotech
Edgard Wood, PhD, Senior Research Director, Discovery, Charles River
2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)
3:10 Close of Conference