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Kinase Inhibitors as drug targets are at the peak of research and development. The pharmaceutical field is now shifting its effort to more non-oncology therapeutic areas. Novel applications for existing inhibitors are being researched and new targets to develop cancer therapeutics are being explored. With over 40% of the projects of large pharma companies in non-oncology areas, there is clearly a need to address the developments and challenges arising.
WEDNESDAY, NOVEMBER 2
7:00 am Conference Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
8:40 Discovery of CX-4945, the First Clinical Stage Inhibitor of Protein Kinase CK2 for the Treatment of Cancer
Fabrice Pierre, Ph.D., Associate Director, Medicinal Chemistry, Cylene Pharmaceuticals, Inc.
Protein kinase CK2 expression and activity are elevated in many cancers, and the enzyme is known to regulate many oncogenic pathways, notably EGFR regulated pathways, PI3K-Akt-mTOR, WNT and NF-kB cascades, angiogenesis and the DNA damage response. These properties make CK2 an attractive oncology target for single-agents or combination therapies. This talk will discuss the design, SAR and latest characterization of CX-4945, the first ATP-competitive inhibitor of CK2 currently in clinical trials.
9:10 Structure-Based Design of VEGFR-2 Inhibitors
Matthew Martin, Ph.D., Senior Scientist, Amgen, Inc.
Using the available structures of VEGFR-2 small molecule complexes, a novel series of inhibitors was identified. This talk will describe the design, optimization, and biological activity of a second generation VEGFR-2 inhibitor.
9:40 Structure-Based Identification of ATP-Competitive MK2 Inhibitors
Arthur Oubrie, CSO, Lead Pharma
MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. In this talk, I will present the structure-based discovery of a novel MK2 inhibitor that exhibited in vivo efficacy in a short-term pre-clinical model. Optimization of this compound led to the identification of inhibitors with improved cellular potency and oral availability.
10:10 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:40 Inhibition of a Novel Serine/Threonine Kinase Over-Expressed in Chronic Obstructive Pulmonary Disorder
Stefen Boehme, Ph.D., Director, Immunology, Axikin Pharmaceuticals, Inc.
We have identified a novel serine/threonine kinase that is upregulated in the lung tissue of COPD patients. siRNA-mediated knock-down of this kinase decreases the secretion of inflammatory cytokines in in vitro experiments and strongly inhibits multiple aspects of the inflammatory response observed in various animal models of COPD. Using the crystal structure of the kinase to guide our screening and SAR efforts, we have identified multiple lead compounds. We will discuss our ongoing pre-clinical development of antagonists against this novel kinase and as a possible treatment for COPD.
11:10 Biochemical and Cellular Profiling of Marketed Kinase Inhibitors
Blaine N. Armbruster, Ph.D., Manager, Lead Discovery, EMD Millipore
This study elucidated the selectivity and cellular activity of several marketed kinase inhibitors, including Imatinib, Sunitinib, Lapatinib. We found that some inhibitors can have unsuspected cellular behavior based on their biochemical profiles.
11:40 Future Fields from Pharma Frustrations?
Dirk Leysen, Ph.D., Founder & CSO, Amakem NV
Kinases are powerful biochemical targets with great potential to treat and modify many diseases. However most kinase inhibitors do not reach the market: systemic side effects limit the dose that can be applied and lead to narrow therapeutic windows and sub-therapeutic treatment regimens. Amakem developed a platform to circumvent these basic problems. Two cases will be presented in the field of ophthalmology and lung diseases that prove the validity of the concept and future value.
12:10 pm Panel Discussion
12:40 Luncheon Presentation:
From cDNA Clones to Assays, A Genomic Approach
Xuan Liu, PhD, Senior Director, Marketing, OriGene Technologies, Inc.
Biomedical research demand quality tools for detection, measurement and perturbation of specific gene/protein targets. Built upon a solid foundation of genome wide full-length cDNA clone clones, OriGene has been developing products and service focusing on system biology approaches to gene function analysis. In this talk, we will showcase some of our novel technology platforms for analyze individual proteins as well as proteome in general.
2:20 Chairperson’s Remarks
2:25 Presentation to be Announced
2:55 Identification of a New Class of c-Met Inhibitors with a Unique Mode of Action and a Distinct Profile Against Activating Mutations
Jason D. Katz, Chemistry Program Team Lead, Department of Chemistry, Merck Research Laboratories
c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes and several activating mutations in the kinase domain of c-Met have been described. This presentation will discuss the identification of MK-2461 and MK-8033, representative of a unique class of c-Met inhibitors that are efficacious in preclinical animal models of tumor progression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase and displays a distinct profile against many of these activating mutations. This presentation will briefly describe the identification of these compounds and discuss potential advantages of their unique characteristics.
3:25 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:05 Multifaceted Intervention by the Hsp90 Inhibitor Ganetespib in Cancers with Activated JAK/STAT Signaling
David Proia, Ph.D., Senior Scientist, Synta Pharmaceuticals Corp.
Persistent JAK/STAT activation is oncogenic and characteristic of many human malignancies and thereby provides an attractive point of intervention for molecularly targeted therapeutics. In this presentation, we show that the Hsp90 inhibitor ganetespib has profound antitumor activity in an array of JAK/STAT-driven cancers and, importantly, can abrogate aberrant signaling through multiple mechanisms.
4:35 A New LIMK Inhibitor Stabilizes Microtubules and has Anticancer Activity
Laurence Lafanechère, Ph.D., Director of Research, CNRS, Team# 03, Polarity, Development & Cancer, Department of Cellular Differentiation and Tansformation, Albert Bonniot Institute
We identified a highly selective cell permeable LIMK inhibitor that reversibly stabilized microtubules and blocked actin microfilament dynamics. We established that the microtubule stabilizing effect of the compound is the result of its inhibitory effect on LIMK, independently of its effect on the actin cytoskeleton. The compound inhibits cell motility and is effective on multidrug resistant cancerous cell lines. It is also effective in animals, where it delays tumors formation while showing a good tolerability.
5:05 Interactive Breakout Discussion Groups
6:15 – 7:15 Welcoming Reception in the Exhibit Hall with Poster Viewing
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