Medicinal Chemistry

When does chemical elaboration induce a ligand to change its binding mode? Malhotra S et al. J Med Chem, 2016, 60(1):128-145.

Application of off-rate screening in the identification of novel pan-isoform inhibitors of pyruvate dehydrogenase kinase. Brough PA et al. J Med Chem, 2017, 60(6):2271-2286.Non-coding RNAs as drug targets. Matsui M et al. Nat Rev Drug Discov, 2017, 16(3):167-179.

Drugging RAS: know the enemy. Papke B et al. Science, 2017, 355(6330):1158-1163.

RON kinase: a target for treatment of cancer-induced bone destruction and osteoporosis. Andrade K et al. Sci Transl Med, 2017, 9(374).

Dual-activity PI3K-BRD4 inhibitor for the orthogonal inhibition of MYC to block tumor growth and metastasis. Andrews FH et al. Proc Natl Acad Sci USA, 2017, 114(7):E1072-E1080.

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies. Kariolis MS et al. J Clin Invest. 2017, 127(1):183-198.

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Kotschy A et al. Nature, 2016, 538(7626):477-482.

Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties. Brust TF et al. Sci Signal, 2017, 10(467).

Synthesis and pharmacological characterization of novel trans-cyclopropylmethyl-linked bivalent ligands that exhibit selectivity and allosteric pharmacology at the dopamine D3 receptor (D3R). Kumar V et al. J Med Chem, 2017, 60(4):1478-1494.

Recent advances in drug discovery of GPCR allosteric modulators for neurodegenerative disorders. Lutjens R  et al. Curr Opin Pharmacol, 2017, 32:91-95.

The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo. Liu C et al. Sci Signal, 2017, 10 (467).

Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists.Zheng Y et al. Nature, 2016, 540(7633):458-461. 

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis. Tran AT et al. Nat Commun, 2017, 8:14414.

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. Oliver JD et al. Proc Natl Acad Sci USA, 2016, Epub ahead of print.

DNA-encoded chemistry: enabling the deeper sampling of chemical space. Goodnow RA Jr et al. Nat Rev Drug Discov, 2017, 16(2):131-147. 

Expanding the cancer arsenal with targeted therapies: disarmament of the antiapoptotic Bcl-2 proteins by small molecules. Yap JL et al. J Med Chem, 2017, 60(3):821-838.

Displacement of drugs from human serum albumin: from molecular interactions to clinical significance. Rimac H et al. Curr Med Chem, 2017, Epub ahead of print.

PDE7-selective and dual inhibitors: advances in chemical and biological research. Jankowska A et al. Curr Med Chem, 2017, Epub ahead of print.

 

Synthetic Chemistry

Unique physicochemical and catalytic properties dictated by the B3NO2 ring system. Noda H et al. Nature Chemistry, 2017, 1-7.

Decarbonylative diaryl ether synthesis by Pd and Ni catalysis. Takise R et al. J Am Chem Soc, 2017, 139(9):3340-3343.

Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group. Yongbing L et al. Nature Chemistry, 2017, 9, 26-32.

Ligand-Enabled beta-C-H arylation of alpha-amino acids without installing exogenous directing groups. Gang C et al. Angewandte Chemie, 2017, 56:1506-1509.

Direct C-H cyanation of arenes via organic photoredox catalysis. Joshua BM et al. J Am Chem Soc, 2017, 139(8):2880-2883.

Strain-release heteroatom functionalization: development, scope, and stereospecificity. Justin ML et al. J Am Chem Soc, 2017, 139(8):3209-3226.

Highly efficient C-H hydroxylation of carbonyl compounds with oxygen under mild conditions. Yu-Feng L et al. Angewandte Chemie, 2014, 53, 548.

Applications of palladium-catalyzed C-N cross-coupling reactions. Paula RC et al. Chemical Reviews, 2016, 116(19):12564-12649.

Aryl amination using ligand-free Ni(II) salts and photoredox catalysis. Corcoran EB et al. Science, 2016, 353(6296):279-283.

Site-selective and stereoselective functionalization of unactivated C-H bonds. kuangbiao L et al. Nature, 2016, 533:230-234.

Formation of a-chiral centers by asymmetric b-C(sp3)-H arylation, alkenylation, and alkynylation. Qing-Feng W et al. Science, 2017, 355(6324):499-503.

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Solid as a Rock: Creating a Strong Foundation for Developing First-in-Class Treatments to Fight Aggressive Cancers – A Chat with Elaine Sullivan, Co-Founder & CEO, Carrick Therapeutics

By Rich Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx)

 

In the life sciences, disruptive innovation is no longer the exception; it’s the rule. One global R&D executive known for successfully driving innovation is Elaine Sullivan.

Sullivan – who has 25 years of experience in the pharma industry – has led R&D teams at Eli Lilly and AstraZeneca, and worked internationally in the US and the UK, developing new molecules in therapy areas such as virology, cancer, ophthalmology, respiratory and inflammation.

Today, she is leading the charge behind Carrick Therapeutics, a start-up whose ambitious plans include becoming Europe’s premier oncology player. Carrick is developing an innovative portfolio of first-in-class treatments that are advanced through understanding the mechanisms that cause cancer and resistance, tailored to an individual patient’s tumor. By linking a network of clinicians and scientists in internationally leading research institutes and hospitals, Carrick plans to use its multi-asset portfolio to drive the development of these ground-breaking cancer therapies from laboratory to clinic.

Carrick has managed to assemble world-class cancer researchers and drug development experts, and has attracted some of the most renowned providers of early stage capital. In October 2016, the company received $95 million in funding, which was led by ARCH Venture Partners and Woodford Investment Management.

I recently spoke with Sullivan, who gave a sneak peek behind Carrick’s new approach to cancer therapies, the company’s strategy in building Europe’s leading oncology company, as well as what drives her passion for science.

Rich Soll: You’ve had such a tremendous rise in the industry. Can you share with us your personal journey?

Elaine Sullivan: I’ve always had a huge passion for science. I was incredibly fortunate to do my Ph.D. with the late Professor Ken Murray, who was one of the founders of Biogen. During that time, he really instilled in me and the group a great belief that everything is possible, and he was one of the most inspirational people I’ve met. To him, life was always about inspiration, biotech, great science, and believing anything’s possible. He was a great mentor and stimulus from the beginning of my career.

Rich Soll: How did your career develop from AstraZeneca and then ultimately lead to Lilly?

Elaine Sullivan: Throughout my career at AstraZeneca, I was really fortunate to be supported in creating and developing functions which were about transformational change in R&D. As vice president, Science & Technology at AstraZeneca, my priority was identifying and integrating novel drug-hunting approaches to successfully reduce compound attrition in the clinic and significantly decrease the time to deliver new molecules.

Then, as vice president, R&D New Opportunities, I established the first virtual therapy area in AstraZeneca to pinpoint new disease areas and future health care trends, create new therapeutic applications for multiple molecular entities, and advance them into the clinic. Getting into the clinic – that’s always the priority.

At Eli Lilly, where I was vice president of Global External Research and Development, the global workforce I led was focused on delivering access to external innovation. We did this, firstly, by identifying, evaluating, and acquiring therapeutic molecules and technologies, and secondly, by creating and managing Lilly’s external R&D portfolio via venture, equity, and strategic partnerships.

Rich Soll: So now we get to Carrick. Carrick is very different in the sense that it’s an outsourced model with key strategic partners; it almost breaks the mold compared to what you’ve been used to, where internal resources were either available or accessible to carry out execution on the projects you were working on. How is Carrick’s model unique?

Elaine Sullivan: One of the cornerstones of Carrick was to create a leading oncology company and to build a company with a strong foundation that we could scale.

We have an excellent, experienced R&D team with an outstanding track record in developing innovative medicines via an outsourced model, collaborating with a network of world class scientists and clinicians in top institutions such as Cambridge University, Imperial College London, Oxford University, and the Christie Hospital in Manchester. Carrick Therapeutics also has a strong association with Cancer Research UK, the world’s leading cancer charity.

In addition, Carrick Therapeutics has assembled a team of internationally recognized clinicians and scientists for the company’s scientific advisory board, which is chaired by Sir John Bell (Regius Professor of Medicine, University of Oxford).

To enable a rapid execution and enhanced selection of compounds across the R&D value chain, we have a unique combination of platform technologies and strategic alliances. That means we can select the best compounds to achieve clinical proof of concept faster and at lower cost.

By pulling our R&D team together, plus the company research engine, we’ve really moved incredibly fast, and we’ve moved quickly because instead of building from scratch the infrastructure and the labs, we’ve almost immediately created a great network of people that have the expertise and facilities at hand. The other advantage we’ve had is that we’ve had enormous support from the scientific community both in Europe and in the US, which has been exceptional.

Carrick is Irish for stone, which represents our vision to create a strong foundation on which to build a successful company.

Rich Soll: What’s interesting to me is you have a terrific investor team and scientific staff. How do you differentiate yourself from other companies in the oncology space?

Elaine Sullivan: For me, the differentiation will always be the science and the compounds that we are progressing. Our initial projects are in aggressive forms of cancer, and adaptive resistance. The projects will have utility in breast, colon, and ovarian cancer, where there is a significant clinical need – for example, the five-year rates of survival are only 50%. We’re passionate about driving change, and with respect to the molecules, the novel mechanisms, our collaborators, and talent we have around us, we feel really confident that we can and will be unique.

Rich Soll: What are your near-term milestones?

Elaine Sullivan: We are getting ready to go into the clinic with a very exciting molecule, and our near-term milestone is to demonstrate a suitable pharmacokinetic and tolerability profile, and then move quickly into an efficacy study to demonstrate a positive effect on patients. We’re also looking for two other clinical assets to accelerate our portfolio build.

Rich Soll: What will Carrick look like three years from now?

Elaine Sullivan: Carrick, in three years’ time, will have compounds that will have read out in the clinic, and we will have continued to move other great projects into the clinic – that’s our clear strategy.

Rich Soll: How important is having the right strategic partners and academic collaborations in fighting these aggressive cancers?

Elaine Sullivan: It’s extremely important because this encourages synergy between us and our collaborators – academic and industry partners – to help us identify those novel signals, and give us that insight into different cancer types and their biological mechanisms. So it’s really important to make sure that the academic partners and Carrick are really linked together, so that when you see something novel you grasp it and incorporate those findings into your R&D programs. That’s what I love; it is hugely exciting.

Rich Soll: We describe cancers historically through several different characteristics, and now we have about 10 characteristics. Do you expect more fundamental additions to this through your own research?

Elaine Sullivan: Yes, I do. We’re working very much on adaptive resistance, and you see that occurring frequently in cancer. It’s about getting in before that resistance kicks in with another molecule, another mechanism. We want to help people live well and long despite their cancer condition.

Rich Soll: Do you see the cancers you’re working on as giving patients longer time or do you see some fundamental breakthroughs in these aggressive cancers that may ultimately lead to cures?

Elaine Sullivan: Of course the ultimate aim is to cure the most advanced forms of aggressive cancer, which is taken as being disease-free after five years. This is sometimes seen for some patients treated with agents designed to target specific molecular changes as we begin to understand the drivers of cancer – for example, Glivec in CML. However, what we’re also trying to do is effect transformational change in cancer care for patients, helping people live well and longer with cancer.

Rich Soll: Are there any personal motivations behind your passionate work with aggressive cancer therapies?

Elaine Sullivan: My father had very aggressive stomach cancer and was given a very poor life expectancy. He was offered a new therapy which included a constant infusion of Fluorouracil (5FU) using a portable pump. He was very brave and was determined to try any treatment that would help him.

His courage and determination to beat the disease was striking, as well as his great humor, which was inspirational. He was intrigued by the therapy, and as an electrical engineer he also worked with the clinical unit to offer suggestions on how to improve the design of the pump. He lived another three years after his diagnosis.  My three children were born during this time and he got know them, which simply wouldn’t have happened if he hadn’t had that treatment. It has hugely affected me, my children, and my whole family.

Rich Soll: What keeps you up at night when you think about Carrick and what you need to accomplish?

Elaine Sullivan: It’s an incredibly exciting opportunity. Carrick is the right company at the right time. What keeps me up at night is thinking about how I can help make sure that the great team and collaborators we have all work together successfully to obtain maximum benefit from our portfolio for cancer patients.

Rich Soll: Do you having any closing thoughts you’d like to share?

Elaine Sullivan: I would just stress that Carrick’s mission is creating Europe’s leading oncology company, and we believe that we have the strong foundation and portfolio that will enable us to achieve our goal. The value of our company is built on our vision and drive to successfully use our portfolio to develop new market-leading treatments, creating transformational change for cancer patients.

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Brave Science: Putting the ‘Hutzpah’ in Early-Stage Drug Discovery – A Chat with Ehud Gazit, Academic Director, Blavatnik Center for Drug Development, Israel

By Rich Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx)

 

From developing new paradigms for early-stage drug discovery for rare and common diseases to fostering the convergence of peptide nanotechnology, and launching scientific experiments in space, Israeli biochemist Ehud Gazit is wearing many hats these days.

In his role as academic director at the newly-formed Blavatnik Center for Drug Discovery (BCDD) at Tel Aviv University in Israel, Gazit is leading efforts to provide the missing link that may enable many scientific discoveries to evolve into beneficial drugs. The Center is uniquely dedicated to translational science by helping researchers turn their discoveries into effective pharmaceuticals.

Gazit – also a biophysicist and nanotechnologist – stays active in his university lab, which explores biological and bio-inspired molecular self-assembly. The lab studies the organization of biological systems in diverse fields, including amyloid diseases, diabetes, virology, and metabolic disorders.

Gazit – who has been a faculty member at Tel Aviv University since 2000, after completing his postdoctoral studies at MIT – also serves as the Chair for Biotechnology of Neurodegenerative Diseases at Tel Aviv University, and heads the Laura Schwartz-Kipp Institute for Biotechnology.

Today, he is also leveraging his former role as the Chief Scientist of the Israeli Ministry of Science and Technology, as well as leadership positions at Tel Aviv University, to bridge science, government, and industry for the greater good of the community.

I recently had an engaging conversation with Gazit, who explained further the mission of the BCDD, his role as a public servant, and how a combination of out-of-the-box-thinking and ‘hutzpah’ can advance science.

Rich Soll: To set the stage, let’s talk a little bit about Israel. The country has several million people and is highly entrepreneurial, highly educated, highly motivated, with professionals in the life sciences and biomedical sciences, and is producing some of the world’s most cutting edge  science and innovative products, which was captured a number of years ago in the book, The Start-Up Nation. In your view, what are some of the top factors that contribute to this disproportionate influence by Israel in the sciences and biomedical research?

Ehud Gazit: I think there are some things that are quite unique that may signify the way that Israel is seen. First, I think it’s out-of-the-box thinking – this is something in Israel that is very clear. Some of it is due to lack of resources.  I remember during my time at MIT, I took these courses on out-of-the-box thinking, and then I realized that maybe Israel needed in-the-box thinking; out-of-the-box thinking comes very natural here.

Secondly, something that may be related to this is the informality which allows Israelis, many time young students and young faculty members, to challenge many of the paradigms. In order to achieve innovation, you need this courage, the hutzpah, to allow yourself to challenge well-known paradigms.

Thirdly, I think it’s the excellent public education system. In Israel, me and most of my graduate students, and my fellow faculty members, we are all products of an excellent public education system, especially the higher education. On a modest budget, we’re able to give first-rate education open to everybody independent of the socio-economic background. This is how you get the most out of the population. I think that every child, even if they grow up in a less favorable environment, deserves and can enjoy a high level education and get into a university – for about $2,000 a year, you get a first-rate education.

Rich Soll: Does having limited resources breed a new way of thinking because you’re faced with this unique challenge?

Ehud Gazit: Yes, you need to be very focused; you need to be very creative. When the resources are limited, indeed, you need to try harder, you need to be focused, and you need to know where you are going. It’s less of a fishing expedition, but rather very directed and precise science.

Rich Soll: Despite having all those limited resources, look at what you’ve done. And your work has such practical consumer implications, such as self-assembly as it relates to fast cell phone charging applications. Can you give us some other examples of this type of work?

Ehud Gazit: We applied a systematic reductionist approach to identify the most fundamental recognition modules in nature. This work had inspired hundreds of groups around the globe to follow our discoveries. Although our quest was for basic biological questions, it turned out to be very important also technologically as some of the minimalistic assembly units form nanostructures with unique mechanical, optical, piezoelectric, pyroelectric and semi-conductive properties. Scientists are very creative in using the nanostructures that we had identified. I have this Google alert on ‘diphenylalanine,’ the module reported in our 2003 Science paper, and every week I get all kinds of applications you couldn’t even think about. This includes the fueling of nano-boats, production of electricity by pressure or heating, and the use of the optical properties to measure very low temperatures like near absolute zero.

Rich Soll: Can you elaborate on some of the themes that you’re examining and the implications of your findings?

Ehud Gazit: We are working on diverse disciplines. One may think that it doesn’t make sense working simultaneously on energy storage devices, superhydrophobic surfaces, biosensors, biomaterials, disease mechanism and drug discovery, but actually they all have a common denominator, which is our quest to understand the most fundamental modules that mediate and facilitate molecular self-assembly at the nano- and micro-scales. I call our research minimalistic and systematic, not biased, so we take complex questions, let’s say recognition by proteins or nucleic acids or other organic molecules, and we try to cut it into the smallest pieces that allow the molecular recognition and self-assembly. It provides us with insights to mechanisms of disease. It helps us to understand how you obtain interesting physical phenomena by identifying these elements. We understand fundamentals of supramolecular polymers chemistry.

One of the things we study is the assembly of structures using the guanine, those parts of DNA and RNA that allow the recognition between the bases. By a systematic, minimalistic, non-biased approach, we go into guanine, which is one of the four nucleobases of DNA, but it is also being extensively used in nature. Evolution has realized over and over again the unique physical properties of guanine assembly. Guanine is the structure that allows the physical coloring of fish, allows chameleons to change their color rapidly, and it serves as reflectors in nocturnal reptiles like crocodiles. We use guanine-based building blocks to obtain various architectures at the nano-scale with remarkable and tunable optical properties.

Rich Soll: I read recently that you were involved in some space rocket experiments. Can you tell us more about that? 

Ehud Gazit: Yes, it’s part of our collaboration with Space Pharma, an Israeli start-up company looking to explore biological activities in space, on the conditions of no gravity. We sent a system based on our small dipeptide system I mentioned and we are trying to see what will be the effect of no gravity on the substance that we put on the physical properties. I do hope that we will see alternative architectures and new physical properties at zero-gravitation conditions.    

Rich Soll: This is outstanding science.  Have new tools and knowledge increased the possibilities and functions of self-assembly?

Ehud Gazit: Yes, one emerging area is the ability of metabolites to self-assemble. It’s been realized for many years that metabolites can crystalize. This is a case of gout, kidney stones, but now we have new tools to understand the formation of the structures, to understand how alternative amyloid-like structures could be formed within the metabolite, and maybe provide new direction to disassemble these structures. We provide new insights into the mechanism of inborn error of metabolism disorders in which there is accumulation of metabolites. So I think, over the last two decades, there has been an important realization from the scientific and medical community of the role of protein self-assembly in neurodegenerative disorders. But I think it’s much wider, looking at molecular self-assembly in general, metabolites, proteins, and lipids.

Rich Soll: So let’s talk more about BCDD. How did it get started and what is its mission?

Ehud Gazit: We’ve been provided with a very generous donation from Len Blavatnik, who is a great supporter of science. Through my experience as a researcher, and as an administrator at a university involved in tech transfer, it became apparent that what is missing in Israel is the very early stage of drug discovery. By engaging in an inclusive, multi-disciplinary environment, we target not only the researchers who are familiar with drug discovery and development, but many others who are excellent scientists but discovered a new biochemical agent, a new receptor, or a new enzyme, but are not familiar with the first steps that could allow these wonderful discoveries to be translated to the development of drugs. In a recent call, we had nearly 30 applications from different fields.

The center is also open to other communities. We often host high school students, very gifted ones, who are being exposed to activities in drug discovery. We also provide information and testing for individuals with rare disease. We are looking for targeted therapy; we try to understand the basic mechanisms of rare disease, and we are in constant dialogue with patient organizations and others. Another activity of the center is organizing conferences. We have had conferences on rare disease, on computer-aided drug design, and drug discovery. We are having another annual meeting on drug discovery and development.

Rich Soll: By being a center, you can draw in research from the university. Is that working so far?

Ehud Gazit:  Yes, we are able to include in the drug discovery community excellent researchers in the university who were not part of drug discovery and development activity. While Tel Aviv University is now doing remarkably well in terms of publications, we are ranked constantly somewhere between 15-to-20 in the world in terms of citations, and have many European Research Council (ERC) grants, even though the number of drug discovery programs is not high.

Through a collaborative approach, we can provide unique service and we can provide our own directions in terms of fragment-based drug development, natural products, and screening for individuals with rare disease. I really want the center to be involved particularly where we have some core expertise that is already appreciated by the industry.

Rich Soll: What do you see as the strengths of the center?

Ehud Gazit: Firstly, it is providing, under one roof in a very efficient way, the full direction needed for drug development beyond the screening, medicinal chemistry and computer-assisted drug design. For many of the projects we have an integrated approach. The center is turning excellent multi-disciplinary science into therapeutic leads. On a daily basis, we sit together – the computation scientists, the high through-put screening specialists, the biologists and the medicinal chemists – in the same room speaking about the challenges, discussing with the faculty members, and people coming from the industry what their needs are. It’s a truly integrative approach.

Secondly, we are located in the middle of the campus, the place for people to stop on their way to their lab, and for students to come by. We are just above the central lecture hall of the university so we have many times students, even freshman, coming to the center to learn about the importance of drug discovery and wanting to be part of this activity.

Thirdly, it is our understanding that you need to provide the full spectrum from basic science to applied science.

Rich Soll: Are there similar centers in Israel? How would you differentiate BCDD versus others?

Ehud Gazit: In Israel there is the National Center for Personalized Medicine at the Weizmann Institute of Science, which provides excellent services, and which we have very good connections with. We see ourselves being more of a research institute and less of a service provider. We try to have our own uniqueness and direction. In our case, there is a stress on an interdisciplinary approach and a close connection to patients. Other centers are excellent and we are coordinating our efforts with them, all for the benefit of science and the benefit of patients.

Rich Soll: You’ve had a very illustrious career –  a great educational background, terrific research, a strong publication record, and then on your career side, rising all the way up to the Chief Scientist  of the Israeli Ministry of Sciences. Can you share your personal journey?

Ehud Gazit: Similar to statistical thermodynamics, these were random walks. I always knew I would be a scientist, but being chief scientist for the Ministry of Science, vice president for research, these things were not planned. As part of my career, I joined Tel Aviv University after my post-doc at MIT. I grew through the ranks, had tenure in two years and became a full professor in about six years. And then I got this offer a very short time after I joined the university, about seven years, to serve as the vice president of research. You cannot refuse such an offer.  I decided, quite to the surprise of many people, to assume also administrative roles. I was vice president of research, and chairman of the technology transfer office, but always keeping my lab active. Then came the offer from the Minister of Science to serve as chief scientist. Again, I could not refuse the offer. It was a way to serve the scientific community; I saw myself as a civil servant.

Rich Soll: What were some of your accomplishments and what lessons did you learn from having these leadership roles?

Ehud Gazit: I learned that science is truly bi-partisan, and something you could get a consensus from left to right, and center. There is an appreciation of the role and importance of science. I also learned that you must motivate players, at the political level and the administration level; you need to motivate people and convince them you can make big changes. I’m not an engineer, but one of the things that I decided was missing in Israel is a type of funding program that is specifically targeted to engineering science. We found so many times that engineers were doing either applied science or very basic science, but less of what I would denoted as ‘engineering science.’  So we established this fund for engineering science.

One of the other things that I pushed forward was international and bilateral agreements between Israel and other countries. I realized that when you convince people about what you do and build up the right coalition, it’s not political, but rather based on the understanding of the importance of things that you think should make a difference. It was really quite an exciting time. Scientists are usually not exposed to government and parliament meetings and hearings. It makes you understand the importance on making science accessible to the general public. You need to let the people understand why they invest so heavily in scientific activities. It’s important to bring the message to the public.

Another thing for me that was very important was to have a public education system in Israel as open as possible to all parts of society, so we have research and development centers all across the country including several in the Arab sector that I specifically supported, as well as special programs for the advancement of women in science.  For me, it was a great opportunity to serve the public at the largest extent.

Rich Soll: How are you implementing those lessons learned to the BCDD?

Ehud Gazit: One thing that I realized is the importance of bringing together people from different disciplines. The BCDD is much about inter-disciplinary, and proving the full spectrum, from basic science to applied science. We also decided to focus on several subjects and one of them is rare disease, in which I see as a remarkable importance from a scientific point of view, but also as a service to society. I see our interaction with the general public, from parents to children with rare disease, for people who carry a mutation and looking for a solution. It is very clear for us that it’s not only about science, but we are there for the people. So in our decision to focus on rare disease and rare disorders, our research is also related to our service to the community.

If I can summarize, you must have excellent basic science in order to have excellent applied science; you can’t take shortcuts. It’s the importance of integrating different disciplines, people from different backgrounds, and the service to the community.

Rich Soll: Looking to the future, what milestones would you like the center to achieve in the next two years?

Ehud Gazit: I hope that we will have several leads related to both common diseases and rare diseases that are less explored. This is a very challenging type of opportunity, since we can’t count on  having a drug come from the center very soon, but if the number of researchers, faculty members,  and graduate students are involved in drug discovery opportunities was doubled or tripled, that would be very important. And I’d like to extend our dialogue with Israeli start-ups in the biomed industry, which needs the help of the academic institutes. Of course, we are truly hoping to get therapeutic leads for various diseases, but we also want to increase the community related to drug discovery both at the university and at the national level.

Rich Soll: So five years from now, what do you think the center would like?

Ehud Gazit: I hope the center, even though it’s still in its infancy, will be a source of excellence for the Tel Aviv University community as well as the community in Israel, and  maybe internationally. I hope that we could provide the scientific community with new paradigms for drug discovery with new methodologies on the development of drugs. I hope that in five years, drug discovery will be a strong point of Tel Aviv University.

Rich Soll: It’s a wonderful set of ambitions. What will it take to achieve these goals?

Ehud Gazit: I think the way to be successful is to be brave, to think big, and to think out-of-the-box. Scientific activity is twofold: on one hand it’s to be the best possible at the state-of-the-arts; you must think at the current state-of-the-art in science.  At the same time, you always have to challenge the known. You have to say, ‘maybe it’s different, maybe I can do it in a different way.’  I try to do this at the center; it is challenging.

Rich Soll: What advice would you give to young scientists?

Ehud Gazit: You must ask the major questions, you must be as good as possible at the science that you do, but you still have to think, ‘maybe I could change things, maybe I could use a different type of mechanism.’ Maybe it’s something beyond what we see. To be a successful scientist you must be brave. You have to believe in what you do. You shouldn’t be disappointed with failure. You should be very happy when you’re experiment is running just as opposite as what you expected.