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SDBN’s #BIO2014 Snapshot 6/5/2014: What’s On Tap, Career Fair, Hangout, Partnering

Posted by Mary Canady June 5th, 2014 .
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2014-06-02 17.48.10

CHI’s Todd Gillenwater, Congressman Scott Peters, and Biocom’s Joe Panetta at the BIO2014 What’s On Tap Event

We’re less than three weeks away from the Biotechnology Industry Organization 2014 convention, can you believe it? Here is our latest summary of news and events:

  • We kicked off June with an event at Karl Strauss in the heart of our biotech sector earlier this week. Congressman Scott Peters, Biocom CEO Joe Panetta, and California Healthcare’s Todd Gillenwater spoke briefly about their excitement about BIO 2014. Panetta spoke about the Digital Health Forum which will showcase San Diego’s strength in this area. Congressman Peters said that even though Congress is in session during the convention, that he’ll be watching and supporting us, as he represents the 52nd District which contains most of our region’s biotech. Karl Strauss did not disappoint with great craft beers and food, and it was very fitting as it has long been the “place to be seen” for San Diego biotech professionals.
  • The BIO 2014 Jobs Career Fair will take place Thursday June 26th and will be a fantastic opportunity for employers and job seekers to connect. Positions in business development, research, finance, marketing, and more will be available. In addition, job seekers who register will get access to the BIO 2014 exhibit hall as well for even more networking. Learn more and register today!
  • We had a great discussion with May 22nd Google Hangout attendees who learned about “Getting The Most Out of #BIO2014 With Social Media & Blogging.” You can view the video by clicking on the title and contact us if you’ve been inspired to start a blog or write for us on the SDBN blog. 
  • SDBN members are very interested in business development and networking and several of you have asked me candidly how to do this best at BIO. I tell them that BIO’s partnering sessions are the best in the industry and highly suggest that attendees choose this option for business development. More than 28,000 meetings will be scheduled, and you can get the most of your partnering meetings with BIO’s in-depth training, which is available on the partnering page linked above. For networking, of course there will be many parties (including the  June 24th SDBN event downtown), and several of the sessions are followed by receptions which will be great for making targeted connections. Sign up soon to attend BIO 2014!
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SDBN’s #BIO2014 Snapshot 5/16/2014

Posted by Mary Canady May 16th, 2014 .
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hc-250x250Here is our latest summary of news and events about the upcoming Biotechnology Industry Organization 2014 convention happening in San Diego June 23-26:

  • Hillary Rodham Clinton Keynote. Former Secretary of State Hillary Rodham Clinton will be the keynote speaker at BIO 2014 on Wednesday June 25. Clinton has been influential in shaping healthcare and foreign policy landscapes, and it will be interesting to hear her perspectives on the biotechnology industry.
  • BIO2014 Press Conference. BIO 2014 COO Scott Whitaker and other representatives visited Janssen Labs in San Diego this week to give a preview of the event, see our review of the event and news coverage here and here. Mayor Kevin Faulconer’s representative Francis Barraza announced that June 23-26 will be BIO week in San Diego!
  • SDBN Google Hangout May 22. BIO 2014 brings a great opportunity for local companies and professionals to shine. A great way to do this is to participate in the conference using social media. On May 22nd, we’ll host a Google Hangout with panelists from SDBN and BIO to show you how to get started blogging or Tweeting about the event. There are many easy ways to get involved, from Tweeting about social events to being a BIO 2014 official blogger. Click here to join us and you’ll learn how you can help spread the news of the convention while getting exposure for yourself and/or your company.

See all of the BIO2014 snapshot posts here.

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Protein-Protein Interactions and Cancer

Posted by Sandeep Pingle May 15th, 2014 .
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p53-bound

Rendering of p53 Tumor Suppressor Bound to DNA. Image courtesy the Protein Data Bank/Research Collaboratory for Structural Bioinformatics.

Protein-protein interactions (PPI) are key regulatory processes in cancer because many proteins that directly interact with binding partners regulate tumor growth. Recognizing this role of PPIs, they have been the focus of recent drug development/discovery efforts. In the recent CHI Drug Discovery Chemistry conference, an entire session of the Protein-Protein Interaction meeting was dedicated to targeting PPI for cancer.

Kurt Deshayes, PhD from Genentech talked about targeting cancer by disrupting PPIs. Of all the hallmarks of cancer described by Hanahan and Weinberg, Deshayes’ targeting focused on the hallmark “evading apoptosis”. Inhibitors of apoptosis (IAP) are a group of proteins that, as the name suggests, inhibit apoptosis. IAP proteins are overexpressed in cancer and represent promising anti-cancer targets. A bivalent IAP antagonist, BV6 was developed as a potent cell death inducer (14 nM IC50). Another small molecule antagonist of IAP, GDC-0152 is being tested and has similar or higher potency against cancer cells.

In addition to IAP, Bcl2- family proteins have been shown to regulate apoptosis. There is a strong correlation between Bcl family member protein expression, tumor growth and resistance to therapy. Consequently, these proteins (binding each other via PPI) have been recently targeted for drug discovery. For example, the BH3 mimetic small molecule, ABT-737 can bind the BIM groove within Bcl-XL and inhibit Bcl2 proteins. In addition, another compound ABT-199 is an effective inhibitor and has been found to have efficacy against primary patient-derived leukemia cells and also clinically in patients.

P53 is a tumor suppressor and it controls pathways that prevent malignant transformation. However, p53 is mutated in >50% of all human cancers and represents a good target for cancer therapy. Daqing Sun from Amgen talked about the discovery of AMG 232, a small molecule inhibitor of the MDM2-p53 interaction. Initial high-throughput screens were used to identify MDM2-p53 inhibitors, which led to the eventual development of AMG 232 that is more potent than most p53 inhibitors currently in clinical development. This compound is being tested in the clinic and may prove to be effective against different cancer types.

Roderick Hubbard from the University of York is currently involved in drug discovery using a fragment-based approach to target PPI. He asserts that fragment-based drug discovery (FBDD) represents “a powerful tool for discovering drug leads”. At this meeting, he mentioned about his work that focused on targeting MDM2-p53 pathway and beta-catenin signaling for cancer. Both these targets yielded success in the form of lead compounds that are being tested for further development. Recently, his team has been working on Bcl2 family proteins, also important in cancer signaling. These various PPIs are highly significant in cancer biology and targeting them for drug discovery using novel approaches like FBDD may yield success.

In spite of the challenges involved, small molecules that interfere with PPIs have been found by different drug discovery methods. Based on the testimony of various scientists from academia and the industry at the Drug Discovery Chemistry meeting, it is obvious that targeting PPIs is “hard work but potentially very fruitful”.

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Targeting Protein-Protein Interactions For Drug Discovery

Posted by Sandeep Pingle May 15th, 2014 .
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PDB_3hsc_EBI

Heat shock protein 70kDa (HSP70), ATPase fragment. Image Courtesy the European Bioinformatics Institute

Cambridge Healthtech Institute (CHI) organizes the annual Drug Discovery Chemistry (DDC) conference that focuses on drug discovery of small molecule candidates and challenges involved in their optimization. True to its motto “Optimizing Small Molecules For Tomorrow’s Therapeutics”, the DDC meeting that was held in San Diego from April 23-25, 2014 focused on multiple drug discovery platforms.

Small molecule drug discovery aims to treat clinical diseases by targeting specific molecules involved in the disease pathway(s). One of the most important targets for drug discovery is protein-protein interaction (PPI). PPIs are associated with a wide range of functions depending on the protein partners involved in the interaction. If two transcription factors interact, this usually leads to DNA binding and subsequent effects on transcription. On the other hand, proteins such as kinases interact and affect downstream signaling. Based on their roles in different diseases, multiple PPIs can be attractive therapeutic targets. The best PPIs for targeting are identified by examining evidence of the biological function in diseases to be addressed.

In spite of their potential as promising targets, PPIs are considered to be “undruggable” or difficult to target. The main reason is that PPI have a high-efficiency binding region for different partners of the protomer. These so-called hotspots may involve large surface areas and may be dictated by multiple different physico-chemical forces that make it difficult to target.

The 7th Annual Protein-Protein Interactions meeting at DDC discussed ways to overcome these limitations and demonstrated promising small molecule inhibitors of PPIs. The chairperson for this meeting, Jason E. Gestwicki, PhD from UC San Francisco introduced the area by describing how chemical biology was being used to develop drugs in the nineties and how the field has developed and matured since then. Further, in his talk, Gestwicki discussed different screening strategies for targeting PPIs, including tethering, fragment-based drug design, structure-based design, and computational modeling-driven drug design. It is important to note that of the various strategies discussed, some PPIs may be more amenable to specific strategies that need to be explored. Gestwicki specifically focused on targeting PPI to inhibit the Heat Shock Protein 90 (Hsp70) complex.

In the same session, Lee Fader from Boehringer Ingelheim Pharmaceuticals talked about allosteric modulators of PPIs with the aim of inhibiting HIV replication. An important step in replication of the virus is capsid assembly. Allosteric inhibitors of capsid assembly have been developed that are being tested for further activity.

Laura Silvian, PhD from Biogen Idec tackled ways to disrupt PPI in the stress response pathway comprising a transcription factor, Nrf2 that binds with another protein KEAP1. The beneficial effects of the Nrf2-KEAP1 pathway are well documented in different areas, including for neuroprotection and immune homeostasis. However, over-activation of the Nrf2 pathway can be deleterious owing to the activation tumor growth. The approach used by researchers to counter the over-activation of this pathway is to disrupt the PPI between Nrf2 and KEAP1 by non-covalent inhibitors. Different non-covalent small molecule inhibitors with varying degrees of potency and efficacy are in the stage of development and show activity comparable to covalent inhibitors.

Recognizing the role of PPIs as novel, promising drug targets, the Protein-Protein Interactions meeting at the DDC conference discussed key strategies and techniques for drug discovery. It went a long way in underlining the significance of this aspect of drug discovery by demonstrating the successes different researchers achieved in this endeavor.

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SDBN’s #BIO2014 Snapshot 4/21/2014

Posted by Mary Canady April 21st, 2014 .
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BIO14_master_ads3Here is our latest snapshot of activities leading up to the Biotechnology Industry Organization (BIO) 2014 convention which will take place in San Diego June 23-26.

Stay tuned for more information and join the SDBN LinkedIn group and sign up for email updates. See all of the BIO2014 snapshot posts here.

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