|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
Translating agile methodology into real-world best practices within the modern software factory has driven widespread DevOps adoption, yet much work remains to expand workflows and tooling across the enterprise. As models evolve from pockets of experimentation into wholescale organizational reinvention, practitioners find themselves challenged to incorporate the culture and architecture necessary to support DevOps at scale. In his session at @DevOpsSummit at 20th Cloud Expo, Anand Akela, Senior...
Apr. 29, 2017 11:15 PM EDT Reads: 2,020
Web Real-Time Communication APIs have quickly revolutionized what browsers are capable of. In addition to video and audio streams, we can now bi-directionally send arbitrary data over WebRTC's PeerConnection Data Channels. With the advent of Progressive Web Apps and new hardware APIs such as WebBluetooh and WebUSB, we can finally enable users to stitch together the Internet of Things directly from their browsers while communicating privately and securely in a decentralized way.
Apr. 29, 2017 11:15 PM EDT Reads: 9,235
In his keynote at @ThingsExpo, Chris Matthieu, Director of IoT Engineering at Citrix and co-founder and CTO of Octoblu, focused on building an IoT platform and company. He provided a behind-the-scenes look at Octoblu’s platform, business, and pivots along the way (including the Citrix acquisition of Octoblu).
Apr. 29, 2017 10:45 PM EDT Reads: 1,783
Multiple data types are pouring into IoT deployments. Data is coming in small packages as well as enormous files and data streams of many sizes. Widespread use of mobile devices adds to the total. In this power panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists will look at the tools and environments that are being put to use in IoT deployments, as well as the team skills a modern enterprise IT shop needs to keep things running, get a handle on all this data, and deli...
Apr. 29, 2017 10:30 PM EDT Reads: 2,765
Grape Up is a software company, specialized in cloud native application development and professional services related to Cloud Foundry PaaS. With five expert teams that operate in various sectors of the market across the USA and Europe, we work with a variety of customers from emerging startups to Fortune 1000 companies.
Apr. 29, 2017 10:15 PM EDT Reads: 2,591
The 20th International Cloud Expo has announced that its Call for Papers is open. Cloud Expo, to be held June 6-8, 2017, at the Javits Center in New York City, brings together Cloud Computing, Big Data, Internet of Things, DevOps, Containers, Microservices and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding business opportunity. Submit your speaking proposal ...
Apr. 29, 2017 10:15 PM EDT Reads: 1,730
Financial Technology has become a topic of intense interest throughout the cloud developer and enterprise IT communities. Accordingly, attendees at the upcoming 20th Cloud Expo at the Javits Center in New York, June 6-8, 2017, will find fresh new content in a new track called FinTech.
Apr. 29, 2017 10:00 PM EDT Reads: 2,630
SYS-CON Events announced today that CollabNet, a global leader in enterprise software development, release automation and DevOps solutions, will be a Bronze Sponsor of SYS-CON's 20th International Cloud Expo®, taking place from June 6-8, 2017, at the Javits Center in New York City, NY. CollabNet offers a broad range of solutions with the mission of helping modern organizations deliver quality software at speed. The company’s latest innovation, the DevOps Lifecycle Manager (DLM), supports Value S...
Apr. 29, 2017 09:45 PM EDT Reads: 1,424
SYS-CON Events announced today that Interoute, owner-operator of one of Europe's largest networks and a global cloud services platform, has been named “Bronze Sponsor” of SYS-CON's 20th Cloud Expo, which will take place on June 6-8, 2017 at the Javits Center in New York, New York. Interoute is the owner-operator of one of Europe's largest networks and a global cloud services platform which encompasses 12 data centers, 14 virtual data centers and 31 colocation centers, with connections to 195 add...
Apr. 29, 2017 09:30 PM EDT Reads: 2,275
The Internet of Things is clearly many things: data collection and analytics, wearables, Smart Grids and Smart Cities, the Industrial Internet, and more. Cool platforms like Arduino, Raspberry Pi, Intel's Galileo and Edison, and a diverse world of sensors are making the IoT a great toy box for developers in all these areas. In this Power Panel at @ThingsExpo, moderated by Conference Chair Roger Strukhoff, panelists discussed what things are the most important, which will have the most profound e...
Apr. 29, 2017 09:30 PM EDT Reads: 2,544
Automation is enabling enterprises to design, deploy, and manage more complex, hybrid cloud environments. Yet the people who manage these environments must be trained in and understanding these environments better than ever before. A new era of analytics and cognitive computing is adding intelligence, but also more complexity, to these cloud environments. How smart is your cloud? How smart should it be? In this power panel at 20th Cloud Expo, moderated by Conference Chair Roger Strukhoff, pane...
Apr. 29, 2017 09:15 PM EDT Reads: 2,549
SYS-CON Events announced today that Hitachi, the leading provider the Internet of Things and Digital Transformation, will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Hitachi Data Systems, a wholly owned subsidiary of Hitachi, Ltd., offers an integrated portfolio of services and solutions that enable digital transformation through enhanced data management, governance, mobility and analytics. We help globa...
Apr. 29, 2017 09:15 PM EDT Reads: 1,556
SYS-CON Events announced today that Grape Up 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. Grape Up is a software company specializing in cloud native application development and professional services related to Cloud Foundry PaaS. With five expert teams that operate in various sectors of the market across the U.S. and Europe, Grape Up works with a variety of customers from emergi...
Apr. 29, 2017 08:30 PM EDT Reads: 2,447
@ThingsExpo has been named the Most Influential ‘Smart Cities - IIoT' Account and @BigDataExpo has been named fourteenth by Right Relevance (RR), which provides curated information and intelligence on approximately 50,000 topics. In addition, Right Relevance provides an Insights offering that combines the above Topics and Influencers information with real time conversations to provide actionable intelligence with visualizations to enable decision making. The Insights service is applicable to eve...
Apr. 29, 2017 08:15 PM EDT Reads: 3,093
SYS-CON Events announced today that Hitachi Data Systems, a wholly owned subsidiary of Hitachi LTD., will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City. Hitachi Data Systems (HDS) will be featuring the Hitachi Content Platform (HCP) portfolio. This is the industry’s only offering that allows organizations to bring together object storage, file sync and share, cloud storage gateways, and sophisticated search an...
Apr. 29, 2017 07:30 PM EDT Reads: 825