Novel Strategies for Kinase Inhibitors  

 

ABOUT THIS CONFERENCE 

Kinases are now well established as a validated drug target class in cancer. However new light is being shed on their role in helping cancers resistant to conventional chemotherapy, representing topics that will be covered within this conference. Attendees will also learn about progress on promising preclinical and early clinical phase kinase inhibitor drug candidates in therapeutic areas beyond cancer, such as inflammation. Another focus of the Novel Strategies for Kinase Inhibitors conference will be on assay development and interpretation for new types of kinase inhibitors such as allosteric modulators and covalent inhibitors.

SUGGESTED EVENT PACKAGE:

 

September 23: New Class of Kinase Inhibitors: Covalent Modifiers Short Course 1 

September 23: Advancing Tools and Technologies for Fragment-Based Design Short Course 5 

September 24-25: Novel Strategies for Kinase Inhibitors Conference 

September 25-26: Cardio-Metabolic Drug Targets Conference 


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Monday, September 23

4:00 - 6:30 pm Early Main Conference Registration


Tuesday, September 24

7:00 am Registration and Morning Coffee


BEYOND CANCER 

8:10 Chairperson’s Opening Remarks

John Robinson, Ph.D., Senior Scientist, Medicinal Chemistry, Array BioPharma Inc.

8:15 Second Generation Janus Kinase Inhibitors

Jordan S. Fridman, Ph.D., Senior Director, Pharmacology, Incyte Corp.

8:45 BTK Inhibitors in Inflammation and Autoimmunity

John Douhan III, Ph.D., Senior Principal Scientist, Immunoscience, Pfizer

In addition to their therapeutic potential in oncology, inhibitors of Bruton’s Tyrosine Kinase (BTK) may prove useful in treating autoimmune disease. The data presented will describe the identification of potent and selective covalent, reversible BTK inhibitors which are efficacious in preclinical models of rheumatoid arthritis and systemic lupus erythematosus.

9:15 ARRY-382, a Selective cFMS inhibitor for the Treatment of Osteolytic Bone Diseases

John Robinson, Ph.D., Senior Scientist, Medicinal Chemistry, Array BioPharma Inc.

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

10:45 Targeting B-Cell Receptor Signaling with PI3Kdelta Inhibitors for Treatment of Inflammatory Diseases and B-cell Malignancies

Kamal PuriKamal Puri, Ph.D., Associate Director, Research, Gilead Sciences, Inc.

GS-1101 is a novel drug that selectively inhibits PI3Kdelta activity and has shown efficacy in clinical trials for the treatment of several types of B-cell malignancies. Emerging preclinical efficacy pharmacology data have shown a critical role of PI3Kdelta in the activation, proliferation, and tissue homing of self-reactive B cells that contribute to autoimmune diseases. Because PI3Kdelta plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, PI3Kdelta inhibitors may represent a promising therapeutic approach for treating these diseases.

EMD Millipore11:15 A Novel Enzyme Reagent for ATM Biochemistry and Drug Discovery Shows High Activity, Purity, and Stability in Screening Assays

Phil_AdamsPhil Adams, Ph.D., Manager, Research & Development, Discovery & Development Solutions, Merck Millipore

EMD Millipore has generated human recombinant ataxia telangiectasia mutated (ATM) protein, full length, and developed an assay for detecting inhibitors of its kinase activity. Here we discuss the ATM enzyme and an assay that monitors its phosphorylation of p53, one of the target substrates for ATM within the cell.

11:45 Deregulated Cdk5-Targeted Inhibitor for Neuro-inflammation

Harish C. Pant, Ph.D., Chief; Laboratory of Cytoskeleton Protein Regulation, National Institute of Neurological Disease and Stroke/ NIH

Cdk5, by virtue of its tightly regulated, multifunctional role in neuronal development, migration, synaptogenesis and survival (it targets a large number of different types of neuronal proteins), has emerged as a major player in neuronal function in health and disease. Our studies continue to unravel the role of Cdk5 in neurogenesis and synaptic function but our most exciting recent results have been related to its role in neurodegeneration and our success in developing compounds that protect neurons from deregulated Cdk5 pathology and apoptosis in vitro and in AD and other neurodegenerative disease model mice. Hence, our current and future plans include a major emphasis on the efficacy of our newly modified peptide TFP5 (carrying a fluorescent marker at the N-terminal end and a TAT PTD sequence at the C-terminal (to facilitate penetration into tissues), as a therapeutic candidate for AD, ALS and PD using model mice. Currently, most therapeutic approaches targeting the deregulated Cdk5/p25 complex in neurodegenerative disorders have focused primarily on drugs like roscovitine that inhibit Cdk5 activity by interfering with the ATP binding domain of the kinase. Most of these drugs, however, lack sufficient specificity, since all kinases including cell cycle Cdks, are vulnerable at the ATP binding site targeted by roscovitine. In previous studies we identified a 124 residue truncated fragment, CIP, derived from the p35 activator, that specifically inhibited hyperactive Cdk5/p25 and rescued cortical cells in vitro from abnormal AD-like phenotypes. It did this without affecting the function of the normal Cdk5/p35. This raised the exciting possibility that CIP might be a therapeutic candidate for the treatment of AD and other neurodegenerative disorders in which hyperactive Cdk5 was implicated. This talk will focus on the role of TFP5 peptide as a therapeutic reagent for AD and ALS.

12:15 pm Orally Available, CNS Penetrant MLK Inhibitors for Treatment of Neurodegenerative Diseases

Val Goodfellow, Ph.D., CEO, Califia Bio, Inc.

We have developed two series of orally available and CNS penetrant mixed lineage kinase inhibitors that have significant activity in animal models of HIV-Associated Neurocognitive Disease. We have developed two classes of compounds, one which inhibits several kinase pathways and one which is quite specific for MLK3. These compounds show contrasting patterns of anti-inflammatory activity and may be useful for treatment of multiple scerosis, Parkinson's disease and heart failure.

12:45 Lunch on Your Own


Allosteric Kinase InhibitorS 

2:15 Chairperson’s Opening Remarks

William J. Pitts, Ph.D., Group Leader, Medicinal Chemistry, Bristol Myers Squibb Co.

2:20 JNK Inhibitor Discovery at Celgene – Tanzisertib and Beyond

Yoshitaka Satoh, Ph.D., Senior Principal Scientist, Medicinal Chemistry,Celgene

The discovery of Tanzisertib, a selective JNK inhibitor which was discontinued during Phase 2 development  in IPF, and our efforts to identify second-generation of JNK inhibitors will be presented.  The attractiveness and challenges of finding a small molecule covalent binder of JNK in comparison to a standard (reversible) approach will be discussed.

2:50 Highly Selective Allosteric FMS Kinase Inhibitors

Bryan SmithBryan Smith, Ph.D., Director, Biology, Deciphera Pharmaceuticals LLC

FMS kinase has been implicated as a major effector of cancer metastasis to bone. FMS signaling is also the primary mechanism whereby tumor-associated macrophages mediate invasiveness and metastasis of a variety of cancers. Deciphera has generated novel allosteric FMS kinase inhibitors, exhibiting extreme selectivity for FMS in a large panel of enzymatic and cellular assays. Lead compounds exhibit profound inhibition of FMS in vivo, and efficacy has been realized in a variety of cancer models. Deciphera’s FMS inhibitors also exhibit exceptional pharmaceutical, pharmacokinetic, and safety profiles.

3:20 LATE BREAKING PRESENTATION: The Design and Optimization of selective PKCθ Inhibitors for the Treatment of MS

Philip Collier Ph.D., Senior Research Scientist, Medicinal Chemistry, Vertex Pharmaceuticals

Protein kinase C theta (PKCθ) has a central role in T cell activation and survival. Studies in PKCθ-deficient mice have demonstrated that whilst anti-viral responses are PKCθ-independent, T cell responses associated with autoimmune diseases are PKCθ- dependent. Thus, selective inhibition of PKCθ is expected to block autoimmune T cell responses without compromising antiviral immunity. The presentation will describe the design and optimization of a novel class of potent and selective PKCθ inhibitors, which show exceptional potency in cells and efficacy in an animal model of MS.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 P529, An Allosteric Modifier of the TORC1 and TORC2 Complexes of the PI3K/Akt/ mTOR Pathway

David SherrisDavid Sherris, Ph.D., President and CEO, Paloma Pharmaceuticals, Inc.

P529 is a first-in-class, allosteric dual dissociative TORC1/TORC2 inhibitor of the PI3K/Akt/mTOR pathway. It has been shown to have broad activity inhibiting the PI3K pathway through multiple sites showing activity in a variety of diseases including age-related macular degeneration and cancer, among other diseases. Discussion will be made on the mechanism of action and results from our Phase I ophthalmic studies.

5:00 Allosterically Targeting Polo-Like Kinase 1 for Selective Cancer Cell Killing

Kyung LeeKyung Lee, Ph.D., Senior Investigator, Section Head, Laboratory of Metabolism, National Cancer Institute

Polo-like kinase 1 (Plk1) is thought to be an attractive anti-cancer drug target selectively required for the viability of activated Ras or inactivated p53-containing cancer cells, but significantly less for the respective normal cells. The C-terminal non-catalytic domain called polo-box domain (PBD) is critically required for the function of Plk1. We present the multi-faceted approaches we've taken to generate a new class of allosteric Plk1 PBD-specific inhibitors.
 


Breakout Discussions


5:30 Interactive Breakout Discussion Groups

This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

In a Class By Themselves: Discovery and Characterization of Allosteric  Modulators of Protein Kinases

Moderator: John Watson, Ph. D., Senior Research Investigator, Bristol-Myers Squibb, Lead Discovery, Evaluation, Profiling and Compound Management

• Why?
-What are the advantages of allosteric modulators for kinases?
-Positive vs. negative allosteric kinase modulators
• Who?
-Are some kinases better suited as targets of allosteric modulators than others?
• How?
-Tweaking assays for identification
-Characterization of modulator properties
-Structural vs. higher throughput approaches
-What can we learn from other target classes? What can other target classes learn from kinases?

Challenges Working with Non-competitive Kinase Inhibitors

Moderator: John Robinson, Ph.D., Senior Scientist, Medicinal Chemistry, Array BioPharma, Inc.

• Do high subcellular ATP levels need to be inhibited? 

• KM v. Raising ATP levels 
• PK/PD – how long to inhibit? 

• How does change in location of inhibitor affect biology? 

Repurposing Kinase Inhibitors

Moderator: Jordan S. Fridman, Ph.D., Senior Director, Pharmacology, Incyte Corp.

• JAK inhibitors -- JAK1 v. JAK2 v. JAK3 v. pan inhibitor  

• Cancer v. inflammation
• Reaching the CNS
 

 

6:30 Welcome Reception in the Exhibit Hall with Poster Viewing 

7:30 Close of Day



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2015 Discovery on Target Brochure  

2015 BROCHURE 


 PREMIER SPONSORS 

Cellecta 

Domainex

Molecular Sensing 

Rosa Drug Development Advisors

Sigma_NEW

 

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IPR_Micrombiome 


SPONSORSHIPS & EXHIBITS 

The exhibit hall was sold out in 2014, so please contact us early to reserve your place. To customize your sponsorship or exhibit package for 2015, contact:

Jon Stroup
Sr. Business Development Manager
781-972-5483
jstroup@healthtech.com 


 

September 21 

Next-Generation Histone Deacetylase Inhibitors Symposia 

Strategies for Rare Diseases Symposia 

September 22 

Developing CRISPR-Based Therapies Symposia 

September 22 - 23 

Targeting Epigenetic Readers and Chromatin Remodelers 

Targeting the Ubiquitin Proteasome System 

Targeting the Microbiome 

GPCR - Based Drug Discovery - Part 1 

Antibodies Against Membrane Protein Targets - Part 1 

RNAi for Functional Genomics Screening 

Gene Therapy Breakthroughs 

Targeting Ocular Disorders 

September 23 - 24 

Targeting Histone Methyltransferases and Demethylases 

Targeting the Unfolded Protein Response 

Kinase Inhibitor Discovery 

GPCR-Based Drug Discovery - Part 2 

Antibodies Against Membrane Protein Targets - Part 2 

New Frontiers in Gene Editing 

Quantitative Systems Pharmacology 

Short Courses 

SC1: Cancer Metabolism: Pathways, Targets and Clinical Updates 

SC2: Leveraging Data and Analytics for Drug DiSCovery 

SC3: Setting Up Effective Rnai SCreens: From Design to Data to Validation 

SC4: Phenotypic SCreening and Chemical Probe Development 

SC5: GPCR Structure-based Drug Discovery 

SC6: Targeting of GPCRs with Monoclonal Antibodies 

SC7: Setting Up Effective Functional SCreens Using 3D Cell Cultures 

SC8: Targeting Protein-protein Interactions: Biophysical Approaches 

SC9: Preclinical Animal Models for Ocular Indications 

SC10: Introduction to Allosteric Modulators and Biased Ligands of GPCRs 

SC11: Introduction to Targeted Covalent Inhibitors 

SC12: Assays and High-throughput SCreening for Novel Epigenetic Inhibitors 

SC13: Gamification and Drug Target Challenges 

SC14: A Primer to Gene Editing: Tools and Applications 

SC15: Using Mechanistic Physiological Models In Drug Development