|By PR Newswire||
|March 5, 2014 08:01 AM EST||
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.
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.
SOURCE DiscoveRx Corporation
Ixia (Nasdaq: XXIA) has announced that NoviFlow Inc.has deployed IxNetwork® to validate the company’s designs and accelerate the delivery of its proven, reliable products. Based in Montréal, NoviFlow Inc. supports network carriers, hyperscale data center operators, and enterprises seeking greater network control and flexibility, network scalability, and the capacity to handle extremely large numbers of flows, while maintaining maximum network performance. To meet these requirements, NoviFlow in...
Jul. 26, 2016 02:00 PM EDT Reads: 507
As companies gain momentum, the need to maintain high quality products can outstrip their development team’s bandwidth for QA. Building out a large QA team (whether in-house or outsourced) can slow down development and significantly increases costs. This eBook takes QA profiles from 5 companies who successfully scaled up production without building a large QA team and includes: What to consider when choosing CI/CD tools How culture and communication can make or break implementation
Jul. 26, 2016 02:00 PM EDT Reads: 1,620
"There's a growing demand from users for things to be faster. When you think about all the transactions or interactions users will have with your product and everything that is between those transactions and interactions - what drives us at Catchpoint Systems is the idea to measure that and to analyze it," explained Leo Vasiliou, Director of Web Performance Engineering at Catchpoint Systems, in this SYS-CON.tv interview at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York Ci...
Jul. 26, 2016 01:45 PM EDT Reads: 1,989
Redis is not only the fastest database, but it is the most popular among the new wave of databases running in containers. Redis speeds up just about every data interaction between your users or operational systems. In his session at 19th Cloud Expo, Dave Nielsen, Developer Advocate, Redis Labs, will share the functions and data structures used to solve everyday use cases that are driving Redis' popularity.
Jul. 26, 2016 12:30 PM EDT Reads: 1,578
UpGuard has become a member of the Center for Internet Security (CIS), and will continue to help businesses expand visibility into their cyber risk by providing hardening benchmarks to all customers. By incorporating these benchmarks, UpGuard's CSTAR solution builds on its lead in providing the most complete assessment of both internal and external cyber risk. CIS benchmarks are a widely accepted set of hardening guidelines that have been publicly available for years. Numerous solutions exist t...
Jul. 26, 2016 11:45 AM EDT Reads: 547
"We're bringing out a new application monitoring system to the DevOps space. It manages large enterprise applications that are distributed throughout a node in many enterprises and we manage them as one collective," explained Kevin Barnes, President of eCube Systems, in this SYS-CON.tv interview at DevOps at 18th Cloud Expo, held June 7-9, 2016, at the Javits Center in New York City, NY.
Jul. 26, 2016 10:45 AM EDT Reads: 1,717
Choosing the right cloud for your workloads is a balancing act that can cost your organization time, money and aggravation - unless you get it right the first time. Economics, speed, performance, accessibility, administrative needs and security all play a vital role in dictating your approach to the cloud. Without knowing the right questions to ask, you could wind up paying for capacity you'll never need or underestimating the resources required to run your applications.
Jul. 26, 2016 10:37 AM EDT Reads: 283
SYS-CON Events announced today that LeaseWeb USA, a cloud Infrastructure-as-a-Service (IaaS) provider, will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. LeaseWeb is one of the world's largest hosting brands. The company helps customers define, develop and deploy IT infrastructure tailored to their exact business needs, by combining various kinds cloud solutions.
Jul. 26, 2016 10:15 AM EDT Reads: 1,179
Adding public cloud resources to an existing application can be a daunting process. The tools that you currently use to manage the software and hardware outside the cloud aren’t always the best tools to efficiently grow into the cloud. All of the major configuration management tools have cloud orchestration plugins that can be leveraged, but there are also cloud-native tools that can dramatically improve the efficiency of managing your application lifecycle. In his session at 18th Cloud Expo, ...
Jul. 26, 2016 10:00 AM EDT Reads: 987
The competitive landscape of the global cloud computing market in the healthcare industry is crowded due to the presence of a large number of players. The large number of participants has led to the fragmented nature of the market. Some of the major players operating in the global cloud computing market in the healthcare industry are Cisco Systems Inc., Carestream Health Inc., Carecloud Corp., AGFA Healthcare, IBM Corp., Cleardata Networks, Merge Healthcare Inc., Microsoft Corp., Intel Corp., an...
Jul. 26, 2016 09:45 AM EDT Reads: 935
SYS-CON Events announced today the Kubernetes and Google Container Engine Workshop, being held November 3, 2016, in conjunction with @DevOpsSummit at 19th Cloud Expo at the Santa Clara Convention Center in Santa Clara, CA. This workshop led by Sebastian Scheele introduces participants to Kubernetes and Google Container Engine (GKE). Through a combination of instructor-led presentations, demonstrations, and hands-on labs, students learn the key concepts and practices for deploying and maintainin...
Jul. 26, 2016 09:45 AM EDT Reads: 767
StackIQ has announced the release of Stacki 3.2. Stacki is an easy-to-use Linux server provisioning tool. Stacki 3.2 delivers new capabilities that simplify the automation and integration of site-specific requirements. StackIQ is the commercial entity behind this open source bare metal provisioning tool. Since the release of Stacki in June of 2015, the Stacki core team has been focused on making the Community Edition meet the needs of members of the community, adding features and value, while ...
Jul. 26, 2016 09:45 AM EDT Reads: 334
Using new techniques of information modeling, indexing, and processing, new cloud-based systems can support cloud-based workloads previously not possible for high-throughput insurance, banking, and case-based applications. In his session at 18th Cloud Expo, John Newton, CTO, Founder and Chairman of Alfresco, described how to scale cloud-based content management repositories to store, manage, and retrieve billions of documents and related information with fast and linear scalability. He addres...
Jul. 26, 2016 09:30 AM EDT Reads: 1,083
Is your aging software platform suffering from technical debt while the market changes and demands new solutions at a faster clip? It’s a bold move, but you might consider walking away from your core platform and starting fresh. ReadyTalk did exactly that. In his General Session at 19th Cloud Expo, Michael Chambliss, Head of Engineering at ReadyTalk, will discuss why and how ReadyTalk diverted from healthy revenue and over a decade of audio conferencing product development to start an innovati...
Jul. 26, 2016 09:15 AM EDT Reads: 1,010
Amazon has gradually rolled out parts of its IoT offerings in the last year, but these are just the tip of the iceberg. In addition to optimizing their back-end AWS offerings, Amazon is laying the ground work to be a major force in IoT – especially in the connected home and office. Amazon is extending its reach by building on its dominant Cloud IoT platform, its Dash Button strategy, recently announced Replenishment Services, the Echo/Alexa voice recognition control platform, the 6-7 strategic...
Jul. 26, 2016 09:02 AM EDT Reads: 245