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Posted in Artificial Intelligence in Medicine - Applications in Therapeutics, Disease Biology, Drug Discovery Chemistry, Machine Learning, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Technology Transfer: Biotech and Pharmaceutical on October 16, 2021| Leave a Comment »

A laboratory for the use of AI for drug development has been launched in collaboration with Pfizer, Teva, AstraZeneca, Mark and Amazon

Reporter: Aviva Lev-Ari, PhD, RN

AION Labs unites pharma, technology and funds companies including IBF to invest in startups to integrate developments in cloud computing and artificial intelligence to improve drug development capabilities. An alliance of four leading pharmaceutical companies –
AION Labs , the first innovation lab of its kind in the world and a pioneer in the process of adopting cloud technologies, artificial intelligence and computer science to solve the R&D challenges of the pharma industry, today announces its launch.
AstraZeneca ,
Mark ,
Pfizer  and
Teva  – and two leading companies in the field of high-tech and biotech investments, respectively – AWS (
Amazon Web Services Inc ) and the Israeli investment fund IBF (
Israel Biotech Fund ) – which joined together to establish groundbreaking ventures Through artificial intelligence and computer science to change the way new therapies are discovered and developed. “We are excited to launch the new innovation lab in favor of discoveries of drugs and medical devices using groundbreaking computational tools,” said Matti Gil, CEO of AION Labs. We are prepared and ready to make a difference in the process of therapeutic discoveries and their development.
With a strong pool of talent from Israel and the world, cloud technology and artificial intelligence at the heart of our activities and a significant commitment by the State of Israel, we are ready to contribute to the health and well-being of the human race and promote industry in Israel.
I thank the partners for the trust, and it is an honor for me to lead such a significant initiative. ”
In addition, AION Labs has announced a strategic partnership with X
BioMed  , an independent biomedical research institute operating in Heidelberg, Germany.
BioMed X has a proven track record in advancing research innovations in the field of biomedicine at the interface between academic research and the pharmaceutical industry.
BioMed X’s innovation model, based on global mass sourcing and incubators to cultivate the most brilliant talent and ideas, will serve as the R & D engine to drive AION Labs’ enterprise model.

SOURCE

הושקה מעבדה לשימוש ב-AI לפיתוח תרופות בשיתוף פייזר, טבע, אסטרהזנקה, מרק ואמזון

https://www.cell.com/iscience/fulltext/S2589-0042(20)31218-9

Posted in COVID-19, Drug Discovery Chemistry, Mechanisms of infection by SARS-CoV-2, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, SARS-CoV-2, Virtual Drug Molecule Screening targeting SAR-CoV-2 proteins, Virus Infective Acute Respiratory Syndrome: SARS-CoV on February 1, 2021| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

ARTICLE|ONLINE NOW, 102021

Open AccessPublished:January 04, 2021DOI:https://doi.org/10.1016/j.isci.2020.102021

SOURCE

The work was made possible in large part by about $1 million in cloud computing hours awarded by Google through a COVID-19 research grant program.

The work reported, below was sponsored by

a Google Cloud COVID-19 research grant. Funding was also provided by the
Fondation Aclon,
National Institutes of Health (GM136859),
Claudia Adams Barr Program for Innovative Basic Cancer Research,
Math+ Berlin Mathematics Research Center,
Templeton Religion Trust (TRT 0159),
U.S. Army Research Office (W911NF1910302), and
Chleck Family Foundation

August 25, 2020 Research

This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

Harvard University and AbbVie today announced a $30 million collaborative research alliance, launching a multi-pronged effort at Harvard Medical School to study and develop therapies against emergent viral infections, with a focus on those caused by coronaviruses and by viruses that lead to hemorrhagic fever.

The collaboration aims to rapidly integrate fundamental biology into the preclinical and clinical development of new therapies for viral diseases that address a variety of therapeutic modalities. HMS has led several large-scale, coordinated research efforts launched at the beginning of the COVID-19 pandemic.

“A key element of having a strong R&D organization is collaboration with top academic institutions, like Harvard Medical School, to develop therapies for patients who need them most,” said Michael Severino, vice chairman and president of AbbVie. “There is much to learn about viral diseases and the best way to treat them. By harnessing the power of collaboration, we can develop new therapeutics sooner to ensure the world is better prepared for future potential outbreaks.”

“The cataclysmic nature of the COVID-19 pandemic reminds us how vital it is to be prepared for the next public health crisis and how critical collaboration is on every level—across disciplines, across institutions and across national boundaries,” said George Q. Daley, dean of Harvard Medical School. “Harvard Medical School, as the nucleus of an ecosystem of fundamental discovery and therapeutic translation, is uniquely positioned to propel this transformative research alongside allies like AbbVie.”

AbbVie will provide $30 million over three years and additional in-kind support leveraging AbbVie’s scientists, expertise and facilities to advance collaborative research and early-stage development efforts across five program areas that address a variety of therapeutic modalities:

Immunity and immunopathology—Study of the fundamental processes that impact the body’s critical immune responses to viruses and identification of opportunities for therapeutic intervention.

Led by Ulirich Von Andrian, the Edward Mallinckrodt Jr. Professor of Immunopathology in the Blavatnik Institute at HMS and program leader of basic immunology at the Ragon Institute of MGH, MIT and Harvard, and Jochen Salfeld, vice president of immunology and virology discovery at AbbVie.

Host targeting for antiviral therapies—Development of approaches that modulate host proteins in an effort to disrupt the life cycle of emergent viral pathogens.

Led by Pamela Silver, the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology in the Blavatnik Institute at HMS, and Steve Elmore, vice president of drug discovery science and technology at AbbVie.

Antibody therapeutics—Rapid development of therapeutic antibodies or biologics against emergent pathogens, including SARS-CoV-2, to a preclinical or early clinical stage.

Led by Jonathan Abraham, assistant professor of microbiology in the Blavatnik Institute at HMS, and by Jochen Salfeld, vice president of immunology and virology discovery at AbbVie.

Small molecules—Discovery and early-stage development of small-molecule drugs that would act to prevent replication of known coronaviruses and emergent pathogens.

Led by Mark Namchuk, executive director of therapeutics translation at HMS and senior lecturer on biological chemistry and molecular pharmacology in the Blavatnik Institute at HMS, and Steve Elmore, vice president of drug discovery science and technology at AbbVie.

Translational development—Preclinical validation, pharmacological testing, and optimization of leading approaches, in collaboration with Harvard-affiliated hospitals, with program leads to be determined.

SOURCE

https://hms.harvard.edu/news/joining-forces

By STEPHANIE DUTCHEN January 28, 2021 Research

This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education, and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

Less than a year ago, Harvard Medical School researchers and international colleagues unveiled a platform called VirtualFlow that could swiftly sift through more than 1 billion chemical compounds and identify those with the greatest promise to become disease-specific treatments, providing researchers with invaluable guidance before they embark on expensive and time-consuming lab experiments and clinical trials.

Propelled by the urgent needs of the pandemic, the team has now pushed VirtualFlow even further, conducting 45 screens of more than 1 billion compounds each and ranking the compounds with the greatest potential for fighting COVID-19—including some that are already approved by the FDA for other diseases.

“This was the largest virtual screening effort ever done,” said VirtualFlow co-developer Christoph Gorgulla, research fellow in biological chemistry and molecular pharmacology in the labs of Haribabu Arthanari and Gerhard Wagner in the Blavatnik Institute at HMS.

The results were published in January in the open-access journal iScience.

The team searched for compounds that bind to any of 15 proteins on SARS-CoV-2 or two human proteins, ACE2 and TMPRSS2, known to interact with the virus and enable infection.

Researchers can now explore on an interactive website the 1,000 most promising compounds from each screen and start testing in the lab any ones they choose.

The urgency of the pandemic and the sheer number of candidate compounds inspired the team to release the early results to the scientific community.

“No one group can validate all the compounds as quickly as the pandemic demands,” said Gorgulla, who is also an associate of the Department of Physics at Harvard University. “We hope that our colleagues can collectively use our results to identify potent inhibitors of SARS-CoV-2.”

In most cases, it will take years to find out whether a compound is safe and effective in humans. For some of the compounds, however, researchers have a head start.

Hundreds of the most promising compounds that VirtualFlow flagged are already FDA approved or being studied in clinical or preclinical trials for other diseases. If researchers find that one of those compounds proves effective against SARS-CoV-2 in lab experiments, the data their colleagues have already collected could save time establishing safety in humans.

Other compounds among VirtualFlow’s top hits are currently being assessed in clinical trials for COVID-19, including several drugs in the steroid family. In those cases, researchers could build on the software findings to investigate how those drug candidates work at the molecular level—something that’s not always clear even when a drug works well.

It shows what we’re capable of computationally during a pandemic.

Hari Arthanari

In another effort to speed successful transitions from computer to clinic, the team has joined in Harvard’s partnership with pharmaceutical company AbbVie.

If any successful drugs eventually arise from the VirtualFlow screens, they would complement other strategies in the fight against COVID-19. For instance, drugs that halt viral replication or prevent it from entering cells could help those who cannot be vaccinated.

The nature of the screens also raises the likelihood that drugs developed against current forms of SARS-CoV-2 would work against future mutations or other coronaviruses, the authors say.

Computing power

The work was made possible in large part by about $1 million in cloud computing hours awarded by Google through a COVID-19 research grant program.

Gorgulla and colleagues used that power to screen how well the compounds bound to more than 40 sites across the 15 viral proteins as well as to the two human proteins—effectively trying 1 billion 3D puzzle pieces in 40 places each.

The team selected the sites because blocking them with compounds would either prevent SARS-CoV-2 from entering cells, prevent the virus from replicating and thus lower viral load, reduce the virus’s ability to evade or subvert our immune defenses, or disrupt viral assembly and packaging.

Many of the sites have not yet been investigated by other groups, as far as the team is aware.

“We’re exploring new avenues on how to tackle the virus. This is one of the most exciting aspects of our project,” said Gorgulla.

One benefit of studying dozens of sites on 17 proteins at once is the possibility of identifying or developing multiple drugs that, when combined, combat SARS-CoV-2 infection on different fronts. Such drug cocktails would have a better chance of halting the virus in its tracks and overcoming future mutations than a single drug that works on one protein site.

Some sites included in the screen are shared among other coronaviruses of worldwide concern. Any compound that binds to one of those sites has a “high” chance of also combating SARS, MERS, or as-yet-unknown coronavirus diseases, said Arthanari.

“We are in a position to discover pan-coronavirus drugs and help prepare for the next coronavirus pandemic, should there ever be one,” said Gorgulla.

Regardless of the outcomes, the work raises the benchmark for virtual screening and demonstrates the current power of computing in biological research.

“It shows what we’re capable of computationally during a pandemic,” said Arthanari.

The project has also brought special satisfaction to team members who don’t typically work on projects so closely tied to human health.

SOURCE

https://hms.harvard.edu/news/screen-door-opens?utm_source=Silverpop&utm_medium=email&utm_term=field_news_item_1&utm_content=HMNews02012021

Posted in Coronavirus Gene Expression, COVID-19, Drug Development Process, Drug Discovery Chemistry, drug repurposing, Personal Health Applications: Tech Innovations serves HealhCare, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, Pharmacogenomics, Pharmacovigilance, Population Health Management, Population Health Management, Genetics & Pharmaceutical, SARS-CoV-2, Serology tests for coronavirus antibodies, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV on May 18, 2020| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

May 18, 2020

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) An Unprecedented Partnership for Unprecedented Times

Francis S. Collins, MD, PhD¹; Paul Stoffels, MD²

Article Information

JAMA. Published online May 18, 2020. doi:10.1001/jama.2020.8920

Author Affiliations

¹Office of the Director, National Institutes of Health, Bethesda, Maryland

²Johnson & Johnson, New Brunswick, New Jersey

It has been more than a century since the world has encountered a pandemic like coronavirus disease 2019 (COVID-19), and the rate of spread of COVID-19 around the globe and the associated morbidity and mortality have been staggering.¹ To address what may be the greatest public health crisis of this generation, it is imperative that all sectors of society work together in unprecedented ways, with unprecedented speed. In this Viewpoint, we describe such a partnership.

First reported in Wuhan, China, in December 2019, COVID-19 is caused by a highly transmissible novel coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). By March 2020, as COVID-19 moved rapidly throughout Europe and the US, most researchers and regulators from around the world agreed that it would be necessary to go beyond “business as usual” to contain this formidable infectious agent. The biomedical research enterprise was more than willing to respond to the challenge of COVID-19, but it soon became apparent that much-needed coordination among important constituencies was lacking.

Clinical trials of investigational vaccines began as early as January, but with the earliest possible distribution predicted to be 12 to 18 months away. Clinical trials of experimental therapies had also been initiated, but most, except for a trial testing the antiviral drug remdesivir,² were small and not randomized. In the US, there was no true overarching national process in either the public or private sector to prioritize candidate therapeutic agents or vaccines, and no efforts were underway to develop a clear inventory of clinical trial capacity that could be brought to bear on this public health emergency. Many key factors had to change if COVID-19 was to be addressed effectively in a relatively short time frame.

On April 3, leaders of the National Institutes of Health (NIH), with coordination by the Foundation for the National Institutes of Health (FNIH), met with multiple leaders of research and development from biopharmaceutical firms, along with leaders of the US Food and Drug Administration (FDA), the Biomedical Advanced Research and Development Authority (BARDA), the European Medicines Agency (EMA), and academic experts. Participants sought urgently to identify research gaps and to discuss opportunities to collaborate in an accelerated fashion to address the complex challenges of COVID-19.

These critical discussions culminated in a decision to form a public-private partnership to focus on speeding the development and deployment of therapeutics and vaccines for COVID-19. The group assembled 4 working groups to focus on preclinical therapeutics, clinical therapeutics, clinical trial capacity, and vaccines (Figure). In addition to the founding members, the working groups’ membership consisted of senior scientists from each company or agency, the Centers for Disease Control and Prevention (CDC), the Department of Veterans Affairs (VA), and the Department of Defense.

Figure.

Accelerating COVID-19 Therapeutic Interventions and Vaccines

NIH-ACTIV’s Working Groups

ACTIV’s 4 working groups, each with one cochair from NIH and one from industry, have made rapid progress in establishing goals, setting timetables, and forming subgroups focused on specific issues (Figure). The goals of the working group, along with a few examples of their accomplishments to date, include the following.

The Preclinical Working Group was charged to standardize and share preclinical evaluation resources and methods and accelerate testing of candidate therapies and vaccines to support entry into clinical trials. The aim is to increase access to validated animal models and to enhance comparison of approaches to identify informative assays. For example, through the ACTIV partnership, this group aims to extend preclinical researchers’ access to high-throughput screening systems, especially those located in the Biosafety Level 3 (BSL3) facilities currently required for many SARS-CoV-2 studies. This group also is defining a prioritization approach for animal use, assay selection and staging of testing, as well as completing an inventory of animal models, assays, and BSL 3/4 facilities.

The Therapeutics Clinical Working Group has been charged to prioritize and accelerate clinical evaluation of a long list of therapeutic candidates for COVID-19 with near-term potential. The goals have been to prioritize and test potential therapeutic agents for COVID-19 that have already been in human clinical trials. These may include agents with either direct-acting or host-directed antiviral activity, including immunomodulators, severe symptom modulators, neutralizing antibodies, or vaccines. To help achieve these goals, the group has established a steering committee with relevant expertise and objectivity to set criteria for evaluating and ranking potential candidate therapies submitted by industry partners. Following a rigorous scientific review, the prioritization subgroup has developed a complete inventory of approximately 170 already identified therapeutic candidates that have acceptable safety profiles and different mechanisms of action. On May 6, the group presented its first list of repurposed agents recommended for inclusion in ACTIV’s master protocol for adaptive clinical trials. Of the 39 agents that underwent final prioritization review, the group identified 6 agents—including immunomodulators and supportive therapies—that it proposes to move forward into the master protocol clinical trial(s) expected to begin later in May.

The Clinical Trial Capacity Working Group is charged with assembling and coordinating existing networks of clinical trials to increase efficiency and build capacity. This will include developing an inventory of clinical trial networks supported by NIH and other funders in the public and private sectors, including contract research organizations. For each network, the working group seeks to identify their specialization in different populations and disease stages to leverage infrastructure and expertise from across multiple networks, and establish a coordination mechanism across networks to expedite trials, track incidence across sites, and project future capacity. The clinical trials inventory subgroup has already identified 44 networks, with access to adult populations and within domestic reach, for potential inclusion in COVID-19 trials. Meanwhile, the survey subgroup has developed 2 survey instruments to assess the capabilities and capacities of those networks, and its innovation subgroup has developed a matrix to guide deployment of innovative solutions throughout the trial life cycle.

The Vaccines Working Group has been charged to accelerate evaluation of vaccine candidates to enable rapid authorization or approval.⁴ This includes development of a harmonized master protocol for adaptive trials of multiple vaccines, as well as development of a trial network that could enroll as many as 100 000 volunteers in areas where COVID-19 is actively circulating. The group also aims to identify biomarkers to speed authorization or approval and to provide evidence to address cross-cutting safety concerns, such as immune enhancement. Multiple vaccine candidates will be evaluated, and the most promising will move to a phase 2/3 adaptive trial platform utilizing large geographic networks in the US and globally.⁵ Because time is of the essence, ACTIV will aim to have the next vaccine candidates ready to enter clinical trials by July 1, 2020.

References

Desai A . Twentieth-century lessons for a modern coronavirus pandemic. JAMA. Published online April 27, 2020. doi:10.1001/jama.2020.4165
Article PubMed Google Scholar

NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19. National Institutes of Health. Published April 29, 2020. Accessed May 7, 2020. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options. National Institutes of Health. Published April 17, 2020. Accessed May 7, 2020. https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options

Corey L , Mascola JR , Fauci AS , Collins FS . A strategic approach to COVID-19 vaccine R&D. Science. Published online May 11, 2020. doi:10.1126/science.abc5312 PubMed Google Scholar

Angus DC . Optimizing the trade-off between learning and doing in a pandemic. JAMA. Published online March 30, 2020. doi:10.1001/jama.2020.4984
Article PubMed Google Scholar

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) portal. National Institutes of Health. Accessed May 15, 2020. https://www.nih.gov/ACTIV

Accelerating Medicines Partnership (AMP). National Institutes of Health. Published February 4, 2014. Accessed May 7, 2020. https://www.nih.gov/research-training/accelerating-medicines-partnership-amp

SOURCE

https://jamanetwork.com/journals/jama/fullarticle/2766371?guestAccessKey=5defc755-e585-47e5-b79a-fee2ec2dd42b&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=051820

Posted in Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Conference Coverage with Social Media, Curation, Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacodynamics and Pharmacokinetics, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, Scientific & Biotech Conferences: Press Coverage, Small Molecules in Development of Therapeutic Drugs, tagged #pharmanews, @Biotech News, AACR, American Association for Cancer Research, Cancer, Estrogen receptor alpha, pharmacokinetic, Pharmacokinetics, real time conference coverage, SHP2, small drug development on April 27, 2020| Leave a Comment »

SESSION VMS.CH01.01 – Advances in Cancer Drug Design and Discovery

April 27, 2020, 11:45 AM – 1:15 PM
Virtual Meeting: All Session Times Are U.S. EDT
DESCRIPTIONAll session times are U.S. Eastern Daylight Time (EDT).

Session Type
Virtual Minisymposium
Track(s)
Cancer Chemistry
14 Presentations
11:45 AM – 11:45 AM
– ChairpersonZoran Rankovic. St. Jude Children’s Research Hospital, Memphis, TN

11:45 AM – 11:45 AM
– ChairpersonChristopher G. Nasveschuk. C4 Therapeutics, Watertown, MA

11:45 AM – 11:50 AM
– IntroductionZoran Rankovic. St. Jude Children’s Research Hospital, Memphis, TN

11:50 AM – 12:00 PM
1036 – Discovery of a highly potent, efficacious and orally active small-molecule inhibitor of embryonic ectoderm development (EED)Changwei Wang, Rohan Kalyan Rej, Jianfeng Lu, Mi Wang, Kaitlin P. Harvey, Chao-Yie Yang, Ester Fernandez-Salas, Jeanne Stuckey, Elyse Petrunak, Caroline Foster, Yunlong Zhou, Rubin Zhou, Guozhi Tang, Jianyong Chen, Shaomeng Wang. Rogel Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, MI, Ascentage Pharma Group, Taizhou, Jiangsu, China

12:00 PM – 12:05 PM
– Discussion

12:05 PM – 12:15 PM
1037 – Orally available small molecule CD73 inhibitor reverses immunosuppression through blocking of adenosine productionXiaohui Du, Brian Blank, Brenda Chan, Xi Chen, Yuping Chen, Frank Duong, Lori Friedman, Tom Huang, Melissa R. Junttila, Wayne Kong, Todd Metzger, Jared Moore, Daqing Sun, Jessica Sun, Dena Sutimantanapi, Natalie Yuen, Tatiana Zavorotinskaya. ORIC Pharmaceuticals, South San Francisco, CA, ORIC Pharmaceuticals, South San Francisco, CA, ORIC Pharmaceuticals, South San Francisco, CA, ORIC Pharmaceuticals, South San Francisco, CA

12:15 PM – 12:20 PM
– Discussion

12:20 PM – 12:30 PM
1038 – A potent and selective PARP14 inhibitor decreases pro-tumor macrophage function and elicits inflammatory responses in tumor explantsLaurie Schenkel, Jennifer Molina, Kerren Swinger, Ryan Abo, Danielle Blackwell, Anne Cheung, William Church, Kristy Kuplast-Barr, Alvin Lu, Elena Minissale, Mario Niepel, Melissa Vasbinder, Tim Wigle, Victoria Richon, Heike Keilhack, Kevin Kuntz. Ribon Therapeutics, Cambridge, MA

12:30 PM – 12:35 PM
– Discussion

12:35 PM – 12:45 PM
1039 – Fragment-based drug discovery to identify small molecule allosteric inhibitors of SHP2. Philip J. Day, Valerio Berdini, Juan Castro, Gianni Chessari, Thomas G. Davies, James E. H. Day, Satoshi Fukaya, Chris Hamlett, Keisha Hearn, Steve Hiscock, Rhian Holvey, Satoru Ito, Yasuo Kodama, Kenichi Matsuo, Yoko Nakatsuru, Nick Palmer, Amanda Price, Tadashi Shimamura, Jeffrey D. St. Denis, Nicola G. Wallis, Glyn Williams, Christopher N. Johnson. Astex Pharmaceuticals, Inc., Cambridge, United Kingdom, Taiho Pharmaceutical Co., Ltd, Tsukuba, Japan

Abstract: The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signalling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Recent advances have shown that genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signalling and inhibits proliferation of RTK-driven cancer cell lines. SHP2 is now understood to act upstream of RAS and plays a role in KRAS-driven cancers, an area of research which is rapidly growing. Considering that RTK deregulation often leads to a wide range of cancers and the newly appreciated role of SHP2 in KRAS-driven cancers, SHP2 inhibitors are therefore a promising therapeutic approach.
SHP2 contains two N-terminal tandem SH2 domains (N-SH2, C-SH2), a catalytic phosphatase domain and a C-terminal tail. SHP2 switches between “open” active and “closed” inactive forms due to autoinhibitory interactions between the N-SH2 domain and the phosphatase domain. Historically, phosphatases were deemed undruggable as there had been no advancements with active site inhibitors. We hypothesised that fragment screening would be highly applicable and amenable to this target to enable alternative means of inhibition through identification of allosteric binding sites. Here we describe the first reported fragment screen against SHP2.
Using our fragment-based Pyramid^TM approach, screening was carried out on two constructs of SHP2; a closed autoinhibited C-terminal truncated form (phosphatase and both SH2 domains), as well as the phosphatase-only domain. A combination of screening methods such as X-ray crystallography and NMR were employed to identify fragment hits at multiple sites on SHP2, including the tunnel-like allosteric site reported by Chen et al, 2016. Initial fragment hits had affinities for SHP2 in the range of 1mM as measured by ITC. Binding of these hits was improved using structure-guided design to generate compounds which inhibit SHP2 phosphatase activity and are promising starting points for further optimization.

anti estrogen receptor therapy: ER degraders is one class
AZ9833 enhances degradation of ER alpha
worked in preclinical mouse model (however very specific)
PK parameters were good for orally available in rodents; also in vitro and in vivo correlation correlated in rats but not in dogs so they were not sure if good to go in humans
they were below Km in rats but already at saturated in dogs, dogs were high clearance
predicted human bioavailability at 40%

12:45 PM – 12:50 PM
– Discussion

12:50 PM – 1:00 PM
1042 – Preclinical pharmacokinetic and metabolic characterization of the next generation oral SERD AZD9833Eric T. Gangl, Roshini Markandu, Pradeep Sharma, Andy Sykes, Petar Pop-Damkov, Pablo Morentin Gutierrez, James S. Scott, Dermot F. McGinnity, Adrian J. Fretland, Teresa Klinowska. AstraZeneca, Waltham, MA

1:00 PM – 1:05 PM
– Discussion

1:05 PM – 1:15 PM
– Closing RemarksChristopher G. Nasveschuk. MA

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Posted in Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, Pharmacogenomics, Rapid automation of plasma protein pools on November 4, 2019| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

4th Advancing Drug Development Forum – Making the Impossible Possible – Harnessing Small Molecule Drug Development scheduled to take place December 12th, 2019 at The University of Massachusetts Club, in Boston, Massachusetts from 8:30 AM – 8:30 PM.

Scientists are more than just chipping away and kicking down the barricades to develop complex small molecule products better and faster. Successful companies are spending quality time finding novel and clever approaches and powerful technologies to better support their knowledgeable teams. Often it takes establishing strong partnerships with 1 or more specialized service providers, cleverly combining resources – always striving to raise the bar in order to make life threatening diseases more of a chronic and tolerable disease or eradicated completely.

Hear from key opinion leaders in pharma, biotech, the investment community and innovative service providers on how they are meeting the challenges. Keep in mind, it takes being open-minded, flexible and willing sometimes to redesigning a new formulation that better enhances bioavailability, optimizes drug-delivery profiles, reduces dosing frequency, or improves the patient experience to have the potential to deliver quicker returns on investments than developing a completely new drug.

PROGRAM AGENDA Thursday, December 12, 2019

8:30 AM Registration and Networking Continental Breakfast

9:00 AM Welcome Address and Opening Remarks
Kevin Bittorf, Ph.D., & Shelly Amster

9:15 AM Opening VC Keynote

9:45 AM Bridging the Gap between Experimentation and Implementation
Panel Discussion

10:15 AM Refreshment Break

10:45 AM Cross-Talk Between Clin-Ops and Tech-Ops
Panel Discussion

11:15 AM The Cost of Speed and Value in Drug Development
Panel Discussion

12:00 PM Networking Luncheon

1:00 PM Advances in the Delivery of Therapeutics to the Brain
Academic Keynote
Mansoor M. Amiji, Ph.D., University Distinguished Professor, Professor of Pharmaceutical Sciences & Professor of Chemical Engineering, Northeastern University

1:30 PM Advancing Drug Delivery and Controlled Release
Panel Discussion

2:00 PM Drowning in DATA

2:30 PM Disruptive AI Technologies Improving Drug Development

3:00 PM Refreshment Break

3:30 PM Small Specialty VS Full Service – What Makes Sense for US?
Panel Discussion

4:00 PM Fireside Chat
Michael Bonney, Executive Chair, Kaleido Biosciences
Heinrich Schlieker, Ph.D., SVP Technical Operations, Sage Therapeutics

5:00 PM – 8:00 PM Networking Social

PROGRAM AGENDA	Thursday, December 12, 2019
8:30 AM		Registration and Networking Continental Breakfast
9:00 AM		Welcome Address and Opening Remarks Kevin Bittorf, Ph.D., & Shelly Amster
9:15 AM		Opening VC Keynote
9:45 AM		Bridging the Gap between Experimentation and Implementation Panel Discussion
10:15 AM		Refreshment Break
10:45 AM		Cross-Talk Between Clin-Ops and Tech-Ops Panel Discussion
11:15 AM		The Cost of Speed and Value in Drug Development Panel Discussion
12:00 PM		Networking Luncheon
1:00 PM		Advances in the Delivery of Therapeutics to the Brain Academic Keynote Mansoor M. Amiji, Ph.D., University Distinguished Professor, Professor of Pharmaceutical Sciences & Professor of Chemical Engineering, Northeastern University
1:30 PM		Advancing Drug Delivery and Controlled Release Panel Discussion
2:00 PM		Drowning in DATA
2:30 PM		Disruptive AI Technologies Improving Drug Development
3:00 PM		Refreshment Break
3:30 PM		Small Specialty VS Full Service – What Makes Sense for US? Panel Discussion
4:00 PM		Fireside Chat Michael Bonney, Executive Chair, Kaleido Biosciences Heinrich Schlieker, Ph.D., SVP Technical Operations, Sage Therapeutics
5:00 PM – 8:00 PM		Networking Social

SOURCE

Direct electronic communication with Shelly Amster

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568558/

Posted in Drug Development Process, Drug Discovery Chemistry, drug repurposing, Pharmaceutical Drug Discovery on February 14, 2019| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN and Irina Robu, PhD

CLAIMER: most valuable information for Drug Repurposing is found in the following LPBI Group three Intellectual Property Asset Classes

Our intellectual property “IP” consists of three classes of assets as described in detail within live links in the below, listed article.

First, the Journal, an ongoing journal of curated, current biomedical research;

Second, the books, a collection of 16 volumes of e-books available via Amazon in five specialties of Medicine: Cardiovascular, Genomics, Cancer, Immunology and Precision Medicine; and

Third, real-time curation of biotech and medical conferences yielding an e-Proceedings at the end of the conference in One-click operation.

These three IP asset classes are described in details with live links in

eScientific Publishing a Case in Point: Evolution of Platform Architecture Methodologies and of Intellectual Property Development (Content Creation by Curation) Business Model

https://pharmaceuticalintelligence.com/2019/02/04/escientific-publishing-a-case-in-point-evolution-of-platform-architecture-methodologies-and-of-intellectual-property-development-content-creation-by-curation-business-model/

M Corsello, Steven & A Bittker, Joshua & Liu, Zihan & Gould, Joshua & McCarren, Patrick & E Hirschman, Jodi & E Johnston, Stephen & Vrcic, Anita & Wong, Bang & Khan, Mariya & Asiedu, Jacob & Narayan, Rajiv & C Mader, Christopher & Subramanian, Aravind & R Golub, Todd. (2017). The Drug Repurposing Hub: A next-generation drug library and information resource. Nature Medicine. 23. 405-408. 10.1038/nm.4306.

… Published on January 3, 2018 as DOI: 10.1124/mol.117. Downloaded from additional source, we used data from the Broad repurposing hub ( Corsello et al, 2017), which employed high throughput screening to characterize drug-target interactions of approved drugs, natural products and nutraceuticals along with other entities. Our analysis yielded a list of currently ‘druggable’ GPCRs and the drugs that target them. …

… Using a range of ~500 (conservative estimate) to ~700 GPCR-targeted drugs, we estimate that between ~25% and ~36% of approved drugs target GPCRs, with the upper figure the more likely. As additional studies such as the Broad repurposing initiative ( Corsello et al, 2017) characterize GPCR-drug interactions in more detail, we anticipate a growth in this number, as secondary interactions between GPCRs and drugs are defined ( Allen and Roth, 2011). IUPHAR lists more druggable GPCRs than CHEMBL or DRUGBANK but has the smallest number of GPCR-related and overall approved drugs ( Figure 3C shows the number of GPCR-targeted drugs based on target-ligand interactions annotated by either IUPHAR or CHEMBL; of the 476 such drugs listed in one or both sources, only a portion are common to both (50%). …

To date there has not been a systematic effort to identify such opportunities, limited in part by the lack of a comprehensive library of clinical compounds suitable for testing. To address this challenge, we hand-curated a collection of 4,707 compounds, experimentally confirmed their identity, and annotated them with literature-reported targets. The collection includes 3,422 drugs that are marketed around the world or that have been tested in human clinical trials. Compounds were obtained from more than 50 chemical vendors and the purity of each sample was established. We have thus established a blueprint for others to easily assemble such a repurposing library, and we have created an online Drug Repurposing Hub (www.broadinstitute.org/repurposing) containing detailed annotation for each of the compounds.

SOURCE

. Author manuscript; available in PMC 2017 Aug 23.

Published in final edited form as:

Nat Med. 2017 Apr 7; 23(4): 405–408.

doi: 10.1038/nm.4306

PMCID: PMC5568558

NIHMSID: NIHMS893143

PMID: 28388612

Steven M. Corsello,^1,^2,³ Joshua A. Bittker,¹ Zihan Liu,¹ Joshua Gould,¹Patrick McCarren,¹ Jodi E. Hirschman,¹ Stephen E. Johnston,¹ Anita Vrcic,¹Bang Wong,¹ Mariya Khan,¹ Jacob Asiedu,¹ Rajiv Narayan,¹Christopher C. Mader,¹ Aravind Subramanian,¹ and Todd R. Golub^1,^3,^4,^5,^*

SOURCE

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568558/

Other Resources

Cancer based pharmacogenomics network supported with scientific evidences: from the view of drug repurposing.[BioData Min. 2015]
Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases.[Drug Des Devel Ther. 2013]
The Resource Hub: an innovative e-information service delivery model addressing mental health knowledge management.[Australas Psychiatry. 2009]
A weighted and integrated drug-target interactome: drug repurposing for schizophrenia as a use case.[BMC Syst Biol. 2015]
Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders.[Schizophr Res Treatment. 2016]

Posted in BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, CANCER BIOLOGY & Innovations in Cancer Therapy, DNA repair, Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, MHC Repertoires for Antigen Prediction, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Discovery on February 6, 2019| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Trovagene announced a new patent for the use of the drug onvansertib in combination with other anti-androgen drugs for the treatment of prostate cancer. Last fall, Trovagene secured exclusive rights to develop combination therapies and clinical biomarkers for prostate cancer based in part on Bridge Project-funded research. Read more.

Lyndra Therapeutics, co-founded by KI member Bob Langer, raised $55 million in its Series B round, with new investors including the Bill and Melinda Gates Foundation and Gilead Sciences. Phase 2 trials for its ultra long-acting drug delivery capsule are expected to begin next year. Read more.

Dragonfly Therapeutics, co-founded by KI director Tyler Jacks, has committed $10 million to launch the first clinical studies of its TriNKETs (Tri-specific, NK cell Engager Therapies) platform for both solid tumor and hematological cancers. Read more.

Following its record-breaking IPO, Moderna Therapeutics (co-founded by KI member Bob Langer) published preclinical data in Science Translational Medicine demonstrating the promise of its mRNA-2752 program in several cancers. Read more.

Dewpoint Therapeutics launched with a $60 million Series A, aims to translate recent insights into biomolecular condensates from the laboratory of co-founder and KI member Rick Young to drug discovery. Read more.

KI member Bob Langer and collaborator Omid Farokhzad co-founded Seer— combining nanotechnology, protein chemistry, and machine learning—to develop liquid biopsy tests for the early detection of cancer and other diseases. Read more.

Epizyme, co-founded by KI member Bob Horvitz, is submitting a New Drug Application to gain accelerated approval of tazemetostat for patients with relapsed or refractory follicular lymphoma. Read more.

Ribon Therapeutics, founded by former KI member Paul Chang, launched with $65 million in a Series B funding round with Victoria Richon, a veteran of Sanofi and Epizyme, at the helm. Ribon focuses on developing PARP7 inhibitors for cancer treatment. Read more.

SOURCE

From: MIT Koch Institute for Integrative Cancer Research <cancersolutions=mit.edu@cmail19.com> on behalf of MIT Koch Institute for Integrative Cancer Research <cancersolutions@mit.edu>

Reply-To: <ki-communications@mit.edu>

Date: Wednesday, February 6, 2019 at 3:15 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Lung Microbiome Corrupted in Cancer; Angelika Amon wins 2019 Vilcek Award; Lunch Lines of Inquiry

Posted in Drug Development Process, Drug Discovery Chemistry, Pharmaceutical Analytics, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Value-based Drug Pricing on February 27, 2018| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

By GlobalData Healthcare

http://pharmaceuticalintelligence.com

Posted in Conference Coverage with Social Media, Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, Pharmacodynamics and Pharmacokinetics, Pharmacogenomics, Pharmacologic toxicities on February 21, 2018| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Dr. Aviva Lev-Ari, PhD, RN, Editor-in-Chief, PharmaceuticalIntelligence.com will be in attendance covering this event for the Press using Social Media via 12 Channels

LOGO of LPBI Group

Our Journal has 1,373,977 eReaders on 1/29/2018, for All Time and 7,283 Scientific Comments

Aviva’s – +6,430 BIOTECH Followers on LinkedIn

http://www.linkedin.com/in/avivalevari

Aviva is a Member of +60 LinkedIn Groups in Biotech related fields

https://www.linkedin.com/groups/my-groups

LPBI Group’s FaceBook Page

http://www.facebook.com/LeadersInPharmaceuticalBusinessIntelligence

https://pharmaceuticalintelligence.com/2016/05/12/preliminary-agenda-available-and-exclusive-discount-to-attend-understanding-crispr-mechanisms-to-applications-symposium-in-boston-september-19-2016

LPBI Group’s Twitter Account

http://twitter.com/pharma_BI

LinkedIn (LI) Group Launcher and Manager of Three LI Groups

Cardiovascular Biotech & Pharma UK & US Networking Group

918 members (1/2018)

Leaders in Pharmaceutical Business Intelligence

342 members (1/2018)

Innovation in Israel

188 members (1/2018)

LPBI Group’s Company’s Page on LinkedIn

https://www.linkedin.com/company/9325543?trk=tyah&trkInfo=clickedVertical%3Acompany%2CclickedEntityId%3A9325543%2Cidx%3A1-1-1%2CtarId%3A1439226813927%2Ctas%3ALeaders%20in%20Pharmaceutica

For PROGRAMS, go to

September 26-27

September 27-28

September 26-27

September 27-28

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September 27-28

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September 25

Leadership we provide on curation of scientific findings in the eScientific publishing for Medical Education contents.

In Section 1, the Leadership we provide on curation of scientific findings in the eScientific publishing for Medical Education contents is demonstrated by a subset of several outstanding curations with high electronic Viewer volume. Each article included presents unique content contribution to Medical Clinical Education.

· These articles are extracted from the list of all Journal articles with >1,000 eReaders, 4/28/2012 to 1/29/2018.

Article Title, # of electronic Viewers, Author(s) Name

Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

16,114

Larry H. Bernstein, MD, FCAP

Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) and PRADAXA (dabigatran)		11,606	Vivek Lal, MBBS, MD, FCIR, Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care		5,865	Aviva Lev-Ari, PhD, RN
Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes	1,919			Aviva Lev-Ari, PhD, RN

Bystolic’s generic Nebivolol – Positive Effect on circulating Endothelial Progenitor Cells Endogenous Augmentation

1,059

Aviva Lev-Ari, PhD, RN

Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

1,339

Aviva Lev-Ari, PhD, RN

Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?	1,472		Aviva Lev-Ari, PhD, RN
Treatment of Refractory Hypertension via Percutaneous Renal Denervation	1,085		Aviva Lev-Ari, PhD, RN

Select

Aviva Lev-Ari, PhD, RN 2012pharmaceutical

3,064 Articles

· All (5,288)

avivalev-ari@alum.berkeley.edu

Administrator

3064

2.1 Volume of Articles in the Journal and in the 16 Volume-BioMed e-Series

1. Volume of Articles in the Journal since Journal inception on 4/28/2012:

· Total articles by ALL authors in Journal Archive on 1/29/2018 = 5,288

· ALL articles/posts Authored, Curated, Reported by Aviva Lev-Ari, PhD, RN = 3,064

2. Volume of Articles in the 16 Volume-BioMed e-Series

· Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-aviva-lev-ari-phd-rn/

· LPBI Group’s Founder: Biography and Bibliographies – Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/founder/

2.2 Digital Presence measured by eViews: Clicks on article by Author Name

Top Authors for all days ending 2018-01-29 (Summarized)

All Time

Author Name		electronic Views
Aviva Lev-Ari, PhD, RN [2012pharmaceutical]		352,153

LPBI Group

1,201

2.3 Digital KOL Parameters

Key Opinion Leader (KOL) – Aviva Lev-Ari, PhD, RN, as Evidenced by

https://pharmaceuticalintelligence.com/2016/07/21/key-opinion-leader-kol-aviva-lev-ari-phd-rn-as-evidenced-by/

L.H. Bernstein, MD, FCAP

Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-larry-h-bernstein-md-fcap/

As BioMed e-Series Editor–in-Chief, I was responsible for the following functions of product design and product launch

· 16 Title creations for e-Books

· Designed 16 Cover Pages for a 16-Volume e-Books e-Series in BioMed

· Designed Series A eTOCs and approved of all 16 electronic Table of Contents (eTOCs), working in tandem with all the Editors of each volume and all the Author contributors of article contents in the Journal.

· Commissioned Articles by Authors/Curators per Author’s expertise on a daily basis

Below, see Volume Titles and Cover Pages:

13 LIVE results for Kindle Store: “Aviva Lev-Ari”

Oct 16, 2017 | Kindle eBook

by Larry H. Bernstein and Aviva Lev-Ari

Subscribers read for free.

$49.00^$ 49 ⁰⁰ to buy Kindle Edition

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Sold by: Amazon Digital Services LLC

May 13, 2017 | Kindle eBook

by Larry H. Bernstein and Demet Sag

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$100.00^$ 100 ⁰⁰ to buy Kindle Edition

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Sep 4, 2017 | Kindle eBook

by Larry H. Bernstein and Aviva Lev-Ari

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Jun 20, 2013 | Kindle eBook

by Margaret Baker PhD and Tilda Barliya PhD

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5 out of 5 stars 6

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Dec 9, 2017 | Kindle eBook

by Larry H. Bernstein and Aviva Lev-Ari

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Nov 28, 2015 | Kindle eBook

by Justin D. Pearlman MD ME PhD MA FACC and Stephen J. Williams PhD

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Nov 29, 2015 | Kindle eBook

by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RN

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Dec 30, 2017 | Kindle eBook

by Larry H. Bernstein and Irina Robu

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Jul 21, 2015 | Kindle eBook

by Larry H. Bernstein MD FCAP and Prabodah Kandala PhD

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5 out of 5 stars 1

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Aug 10, 2015 | Kindle eBook

by Larry H Bernstein MD FCAP and Prabodh Kumar Kandala PhD

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Nov 22, 2015 | Kindle eBook

by Sudipta Saha PhD and Ritu Saxena PhD

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Dec 26, 2015 | Kindle eBook

by Larry H. Bernstein MD FACP and Aviva Lev-Ari PhD RN

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Dec 26, 2015 | Kindle eBook

by Justin D. Pearlman MD ME PhD MA FACC and Ritu Saxena PhD

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