Welcome!

News Feed Item

Research by Structural Genomics Consortium and DiscoveRx Points to New Multi-Targeting Approaches to Cancer Therapy

Joint Publication Identifies Clinical Kinase Inhibitors that Potently Cross React with Bromodomain Epigenetic Reader Proteins

OXFORD, United Kingdom and FREMONT, Calif., March 5, 2014 /PRNewswire/ -- The Structural Genomics Consortium (SGC) and DiscoveRx Corporation today announced the publication of findings that suggest compelling new multi-targeting approaches for cancer therapy. In a study entitled "Dual kinase-bromodomain inhibitors for rationally designed polypharmacology," which appeared on-line in Nature Chemical Biology (http://www.nature.com/nchembio/index.html), the researchers demonstrate that several clinical kinase inhibitors also potently inhibit diverse bromodomain epigenetic reader proteins.

DiscoveRx Corporation, Fremont, CA, Contact: Sailaja Kuchibhatla, skuchibhatla@discoverx.com

Kinase inhibitor-based targeted therapies have had clinical successes. However, a substantial proportion of patients fail to respond initially, and acquired resistance to these drugs remains problematic. Inhibition of multiple oncogenic proteins in the same tumor is an established strategy to address these challenges, but the discovery of inhibitors targeting multiple rationally chosen kinases is difficult, and combination therapy approaches require complex clinical investigations.

The finding that several oncology-focused clinical kinase inhibitors also potently inhibit bromodomains, including the established cancer target BRD4, demonstrates the feasibility of a "single agent, inter-family" multi-targeting approach. The structural biology data presented indeed suggest actionable dual inhibitor design strategies. Co-senior author Stefan Knapp, Principal Investigator at the SGC (based at the University of Oxford) commented, "The diversity of the kinase catalytic site and the acetyllysine binding pockets in bromodomains will allow optimization of inhibitor potency for both target classes, which will facilitate the development of therapeutic dual inhibitors."

Among the kinase inhibitors shown to have potent BRD4 activity are the JAK2-FLT3 inhibitor TG-101348 and the PLK1 inhibitors BI-2536 and volasertib. "Since FLT3 and BRD4 can be independent drivers in acute myelogenous leukemia, the TG-101348 data raise hope for the development of an optimized dual FLT3-BRD4 inhibitor, which would be anticipated to improve patient outcomes," said co-senior author Daniel Treiber, Sr. Director of Research at DiscoveRx.

Co-author Neil Shah, Leader of the Hematopoietic Malignancies Program at the UCSF Helen Diller Family Comprehensive Cancer Center, agrees that multi-targeting single agent therapies could offer significant advantages. "Attempts to clinically test therapeutic combination strategies that exploit synergistic interactions are often hampered by significant obstacles such as the potentially unacceptable cost and toxicity of combining two drugs, as well as practical difficulties inherent in working simultaneously with two pharmaceutical companies," he said. "This work excitingly demonstrates that in some cases, rational medicinal chemistry efforts can circumvent many of these issues and potentially rapidly advance medical science."

Importantly, the dual BRD4-kinase inhibitors were also shown to exhibit complex, unique polypharmacologies across a panel of human primary cell disease models (BioMAP® systems). "Our strategy of using both target-based and phenotypic screening approaches represents a paradigm shift in developing single agents that can act as ready-made combination therapies that may be more efficacious and overcome clinical obstacles," said co-first author Alison O'Mahony, Sr., Director of Research at BioSeek, a division of DiscoveRx.

About the Structural Genomics Consortium
The Structural Genomics Consortium (SGC) (http://www.thesgc.org/) is a not-for-profit, public-private partnership that conducts pre-competitive research to facilitate the discovery of new medicines.  Based at the University of Oxford and University of Toronto the SGC's work contributes to new hypotheses in understanding and treating human disease, and the subsequent identification of new targets for drug discovery. The SGC's primary objectives are to produce and characterize the 3-dimensional structures of soluble proteins and of integral membrane proteins, to generate selective chemical probes for epigenetic proteins and kinases, and to release these into the public domain. As part of its mission the SGC generates medically relevant reagents and knowledge related to human proteins and proteins from human parasites, which it shares through over 250 collaborations with researchers worldwide. Since 2004 the SGC has solved over 1400 protein structures and has generated 19 chemical probes for epigenetic proteins (http://www.thesgc.org/chemical-probes/epigenetics).

About DiscoveRx Corporation
Founded in 2000, DiscoveRx is a leading provider of next generation drug discovery screening and profiling platforms. Utilizing its three proprietary technology platforms beta-galactosidase-based enzyme fragment complementation (EFC), KINOMEscan® and BioMAP® (http://www.biomapsystems.com), DiscoveRx offers an industry leading portfolio of over 1000 target-based and human primary cell-based systems for oncology, metabolic disease, inflammation, autoimmunity, CNS and cardiovascular research at global pharmaceutical, biotechnology and academic institutes.  For more information, visit http://www.discoverx.com.

University of California Disclaimer
The information stated above was prepared by the Structural Genomics Consortium (SGC) and DiscoveRx Corp. and reflects solely that opinion. Nothing in this statement shall be construed to imply any support or endorsement of the SGC or DiscoveRx, or any of its products, by The Regents of the University of California, its officers, agents and employees.

Logo - http://photos.prnewswire.com/prnh/20130912/SF78575LOGO

SOURCE DiscoveRx Corporation

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
When it comes to cloud computing, the ability to turn massive amounts of compute cores on and off on demand sounds attractive to IT staff, who need to manage peaks and valleys in user activity. With cloud bursting, the majority of the data can stay on premises while tapping into compute from public cloud providers, reducing risk and minimizing need to move large files. In his session at 18th Cloud Expo, Scott Jeschonek, Director of Product Management at Avere Systems, discussed the IT and busine...
Organizations do not need a Big Data strategy; they need a business strategy that incorporates Big Data. Most organizations lack a road map for using Big Data to optimize key business processes, deliver a differentiated customer experience, or uncover new business opportunities. They do not understand what’s possible with respect to integrating Big Data into the business model.
Enterprises have taken advantage of IoT to achieve important revenue and cost advantages. What is less apparent is how incumbent enterprises operating at scale have, following success with IoT, built analytic, operations management and software development capabilities – ranging from autonomous vehicles to manageable robotics installations. They have embraced these capabilities as if they were Silicon Valley startups. As a result, many firms employ new business models that place enormous impor...
Amazon is pursuing new markets and disrupting industries at an incredible pace. Almost every industry seems to be in its crosshairs. Companies and industries that once thought they were safe are now worried about being “Amazoned.”. The new watch word should be “Be afraid. Be very afraid.” In his session 21st Cloud Expo, Chris Kocher, a co-founder of Grey Heron, will address questions such as: What new areas is Amazon disrupting? How are they doing this? Where are they likely to go? What are th...
SYS-CON Events announced today that MIRAI Inc. will exhibit at the Japan External Trade Organization (JETRO) Pavilion at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. MIRAI Inc. are IT consultants from the public sector whose mission is to solve social issues by technology and innovation and to create a meaningful future for people.
SYS-CON Events announced today that Dasher Technologies will exhibit at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 - Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Dasher Technologies, Inc. ® is a premier IT solution provider that delivers expert technical resources along with trusted account executives to architect and deliver complete IT solutions and services to help our clients execute their goals, plans and objectives. Since 1999, we'v...
SYS-CON Events announced today that NetApp has been named “Bronze Sponsor” of SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. NetApp is the data authority for hybrid cloud. NetApp provides a full range of hybrid cloud data services that simplify management of applications and data across cloud and on-premises environments to accelerate digital transformation. Together with their partners, NetApp emp...
Though cloud is the future of enterprise computing, a smooth transition of legacy applications and systems is critical for seamless business operations. IT professionals are eager to start leveraging the cost, scale and other benefits of cloud, but with massive investments already in place in existing infrastructure and a number of compliance and resource hurdles, it can be challenging to move to a cloud-based infrastructure.
In his session at 21st Cloud Expo, Raju Shreewastava, founder of Big Data Trunk, will provide a fun and simple way to introduce Machine Leaning to anyone and everyone. Together we will solve a machine learning problem and find an easy way to be able to do machine learning without even coding. Raju Shreewastava is the founder of Big Data Trunk (www.BigDataTrunk.com), a Big Data Training and consulting firm with offices in the United States. He previously led the data warehouse/business intellige...
SYS-CON Events announced today that IBM has been named “Diamond Sponsor” of SYS-CON's 21st Cloud Expo, which will take place on October 31 through November 2nd 2017 at the Santa Clara Convention Center in Santa Clara, California.
SYS-CON Events announced today that TidalScale, a leading provider of systems and services, will exhibit at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 - Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. TidalScale has been involved in shaping the computing landscape. They've designed, developed and deployed some of the most important and successful systems and services in the history of the computing industry - internet, Ethernet, operating s...
Infoblox delivers Actionable Network Intelligence to enterprise, government, and service provider customers around the world. They are the industry leader in DNS, DHCP, and IP address management, the category known as DDI. We empower thousands of organizations to control and secure their networks from the core-enabling them to increase efficiency and visibility, improve customer service, and meet compliance requirements.
In his session at 21st Cloud Expo, Michael Burley, a Senior Business Development Executive in IT Services at NetApp, will describe how NetApp designed a three-year program of work to migrate 25PB of a major telco's enterprise data to a new STaaS platform, and then secured a long-term contract to manage and operate the platform. This significant program blended the best of NetApp’s solutions and services capabilities to enable this telco’s successful adoption of private cloud storage and launchi...
SYS-CON Events announced today that IBM has been named “Diamond Sponsor” of SYS-CON's 21st Cloud Expo, which will take place on October 31 through November 2nd 2017 at the Santa Clara Convention Center in Santa Clara, California.
Data scientists must access high-performance computing resources across a wide-area network. To achieve cloud-based HPC visualization, researchers must transfer datasets and visualization results efficiently. HPC clusters now compute GPU-accelerated visualization in the cloud cluster. To efficiently display results remotely, a high-performance, low-latency protocol transfers the display from the cluster to a remote desktop. Further, tools to easily mount remote datasets and efficiently transfer...