Archive for the ‘Pharmaceutical Drug Discovery’ Category

Personalized Medicine been Positively affected by FDA Drug Approval Record

Reporter: Aviva Lev-Ari, PhD, RN

FDA to Clear Path for Drugs Aimed at Cancer-Causing Genes

By Anna Edney and Michelle Cortez

June 20, 2017, 10:41 AM EDT June 20, 2017, 3:02 PM EDT



‘Landmark FDA approval bolsters personalized medicine’

PMC – An Op-Ed in STAT News

by Edward Abrahams

June 21, 2017

Our understanding of cancer has been morphing from a tissue-specific disease — think lung cancer or breast cancer — to a disease characterized more by specific genes or biomarkers than by location. A recent FDA decision underscores that transition and further opens the door to personalized medicine.

Two years ago, the director of the FDA’s Office of Hematology and Oncology Products told the Associated Press that there was no precedent for the agency to approve a drug aimed at treating tumors that generate a specific biomarker no matter where the cancer is in the body. Such a drug had long been seen as the epitome of personalized medicine. But with the rapid pace of progress in the field, director Dr. Richard Pazdur said, such an approval could one day be possible.

That day has arrived.

In a milestone decision for personalized medicine, the FDA approved Merck’s pembrolizumab (Keytruda) late last month for the treatment of tumors that express one of two biomarkers regardless of where in the body the tumors are located. The decision marks the first time FDA has approved a cancer drug for an indication based on the expression of specific biomarkers rather than the tumor’s location in the body.

Keytruda is designed to help the immune system recognize and destroy cancer cells by targeting a specific cellular pathway. The FDA notes that the two biomarkers — microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) — affect the proper repair of DNA inside cells.

The approval represents an important first for the field of personalized medicine, which anticipates an era in which physicians use molecular tests to classify different forms of cancer based on the biomarkers they express, then choose the right treatment for it. In contrast to standard cancer treatments, which are given to large populations of patients even though only a fraction of them will benefit, Keytruda was approved only for the 4 percent of cancer patients whose tumors exhibit MSI-H or dMMR mutations. That may help the health system save money by focusing resources only on patients who are likely to benefit from Keytruda.

Such “personalized” strategies now dominate the landscape for cancer drug development. Personalized medicines account for nearly 1 of every 4 FDA approvals from 2014 to 2016, and the Tufts Center for the Study of Drug Development estimates that more than 70 percent of cancer drugs now in development are personalized medicines.

While this is encouraging, the U.S. research, regulatory, and reimbursement systems aren’t aligned to stimulate the development of personalized medicines, and may even deter progress.

The Trump administration’s proposal to cut biomedical research spending at the National Institutes of Health by 18 percent in fiscal year 2018, for example, would undermine its ability to fund more studies like the National Cancer Institute’s Molecular Analysis for Therapy Choice (MATCH) trial, which is designed to test targeted therapies across tumor types.

While the regulatory landscape for these targeted medicines is clear, the path to market for the molecular tests that do the targeting is not. That uncertainty continues to stifle investment in the innovative tests that make personalized medicine possible. The result is a clinical environment in which the patients who could benefit from personalized medicines are often never identified because the necessary tests aren’t available to them.

Finally, increasing pressure on pharmaceutical and diagnostic companies to decrease prices without considering their value to individual patients and the health system could also deter investment in innovative solutions that address unmet medical needs, particularly for smaller patient populations.

Confronted with unprecedented opportunities in personalized medicine, policymakers would do well to ensure that our research, regulatory, and reimbursement systems facilitate the development of and access to these promising new therapies. Only then can we ensure that Keytruda’s groundbreaking approval represents the beginning of a new era that promises better health and a more cost-effective health system.

Edward Abrahams, Ph.D., is president of the Personalized Medicine Coalition.





From: <>

Date: Wednesday, June 21, 2017 at 1:38 PM

To: Aviva Lev-Ari <>

Subject: PMC in STAT: “Landmark FDA Approval Bolsters Personalized Medicine”


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Pharmacotyping Pancreatic Cancer Patients in the Future: Two Approaches – ORGANOIDS by David Tuveson and Hans Clevers and/or MICRODOSING Devices by Robert Langer

Curator: Aviva Lev-Ari, PhD, RN


UPDATED on 4/5/2018

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MIT News Office
March 27, 2018


This curation provides the resources for edification on Pharmacotyping Pancreatic Cancer Patients in the Future


  • Professor Hans Clevers at Clevers Group, Hubrecht University

  • Prof. Robert Langer, MIT

Langer’s articles on Drug Delivery

organoids, which I know you’re pretty involved in with Hans Clevers. What are your plans for organoids of pancreatic cancer?

Organoids are a really terrific model of a patient’s tumour that you generate from tissue that is either removed at the time of surgery or when they get a small needle biopsy. Culturing the tissue and observing an outgrowth of it is usually successful and when you have the cells, you can perform molecular diagnostics of any type. With a patient-derived organoid, you can sequence the exome and the RNA, and you can perform drug testing, which I call ‘pharmacotyping’, where you’re evaluating compounds that by themselves or in combination show potency against the cells. A major goal of our lab is to work towards being able to use organoids to choose therapies that will work for an individual patient – personalized medicine.

Organoids could be made moot by implantable microdevices for drug delivery into tumors, developed by Bob Langer. These devices are the size of a pencil lead and contain reservoirs that release microdoses of different drugs; the device can be injected into the tumor to deliver drugs, and can then be carefully dissected out and analyzed to gain insight into the sensitivity of cancer cells to different anticancer agents. Bob and I are kind of engaged in a friendly contest to see whether organoids or microdosing devices are going to come out on top. I suspect that both approaches will be important for pharmacotyping cancer patients in the future.

From the science side, we use organoids to discover things about pancreatic cancer. They’re great models, probably the best that I know of to rapidly discover new things about cancer because you can grow normal tissue as well as malignant tissue. So, from the same patient you can do a comparison easily to find out what’s different in the tumor. Organoids are crazy interesting, and when I see other people in the pancreatic cancer field I tell them, you should stop what you’re doing and work on these because it’s the faster way of studying this disease.


Other related articles on Pancreatic Cancer and Drug Delivery published in this Open Access Online Scientific Journal include the following:


Pancreatic Cancer: Articles of Note

Curator: Aviva Lev-Ari, PhD, RN

Keyword Search: “Pancreatic Cancer” – 275 Article Titles

Keyword Search: Drug Delivery: 542 Articles Titles

Keyword Search: Personalized Medicine: 597 Article Titles

  • Cancer Biology & Genomics for Disease Diagnosis, on Amazon since 8/11/2015




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Exosomes: Natural Carriers for siRNA Delivery

Author(s): Lalit Kumar, Shivani Verma, Bhuvaneshwar Vaidya, Vivek Gupta.


Various cells of the human physiological system have the capability to release extracellular vesicles (EVs) involved in intercellular transport of proteins and nucleic acids. Exosomes are a subtype of extracellular vesicles having their origin through endocytic pathway. While being involved in intercellular transport of macromolecules, exosomes, due to their presence in several body fluids, can also be utilized as a system to commute RNA molecules and proteins in the body. Recent advances in gene therapy have provided a new outlook in disease therapeutics by modulation of gene expression using oligonucleotide based approach and exosomes have been reported a potential carrier for nucleic acid based therapeutic moieties. In recent years, small interfering RNA (siRNA) has emerged as promising therapeutic alternative for diseases with gene-based pathophysiology, however poor bioavailability limits its therapeutic potential. For effective delivery and enhancement of bioavailability of siRNA, several carriers including dendrimers, liposomes, siRNA conjugates, and siRNA aptamer chimeras, to name a few, have been explored. Exosomes can be considered a promising carrier for effective delivery of siRNA due to their existence in body’s endogenous system and high tolerance. The present review focuses on delivering knowledge about exosomes, siRNA, and capability of exosomes to act as natural carriers for siRNA delivery.

Keywords: Extracellular vesicles, endogenous, exosomes, oligonucleotide, small interfering RNA.

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Article Details

Year: 2015
Page: [4556 – 4565]
Pages: 10
DOI: 10.2174/138161282131151013190112
Price: $58


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VC Investment in BioTech MegaHubs and Top R&D Spenders among Big Pharma

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 4/26/2017

The top 10 pharma R&D budgets in 2016

The Top 10 Pharma R&D Budgets in 2016

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Book traversal links for The top 10 pharma R&D budgets in 2016




Table SOURCE: Thomson Reuters abd ENDPOINTS

According to both sources:

  • $3.5 billion for Silicon Valley plus the Bay Area and
  • $2.8 billion for New England.

Broken down by city, $6.1 billion went to

  • Boston ($2.7 billion),
  • San Jose ($2.5 billion) and
  • San Francisco/Berkeley ($1 billion).
  • San Diego ($725 million),
  • New York ($454 million) and
  • the Great Lakes area ($412 million)


Where the money is: Biotech’s megahubs command VC’s billions by john carrollJune 30, 2016 10:41 AM EDT, Updated: November 17, 2016 07:32 PM

The top 15 spenders in the global drug R&D business: 2017

by john carroll

April 24, 2017 05:22 AM EDT, Updated: 05:27 AM

The top five in the business saw their collective spending jump by more than $5 billion, from 2015 to 2016, based on the annual numbers filed largely — though not entirely — with the SEC and gathered by Endpoints News. Two of those companies,

  • Roche and the new number 2, a hard charging
  • Merck, accounted for the lion’s share of the increase. (To be sure, some onetime non-R&D spending, such as Merck’s patent settlement with Bristol-Myers on Keytruda, figured in. But so did bread and butter spending.)
  • Gilead also saw a significant increase in research costs, with
  • Eli Lilly — now off course following two bad setbacks for solanezumab and baricitinib — and the ever aggressive
  • Celgene joining the action as they pressed the accelerator on new drug programs.

Curiously, the added spending coincided with a bad drop in new drug approvals in 2016. But they don’t correlate, and we’ve already seen that turnaround under way as regulators get busy with a brand new year — and soon a brand new FDA commissioner.


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World’s Top Ten Cancer Drugs by 2020  (million USD)

Reporter: Aviva Lev-Ari, PhD, RN



Image Source: Statista (

Opdivo Setback May Yield Lessons for Pharma – Advancing Immunotherapies With PD-L1 Testing

Sep 12, 2016 | Turna Ray

The anti-PD-1/PD-L1 drug market is estimated to be worth around $30 billion by 2020. The negative Phase III results for Opdivo in first-line NSCLC shocked market analysts, and pharmaceutical companies developing drugs in this space “are taking stock of the situation” and surely assessing whether they have the right test methods in place in their drug studies, said Peter Keeling, CEO of consulting firm Diaceutics.

Most drugmakers developing anti-PD-1/PD-L1 drugs are evaluating whether their therapies work especially well in patients whose tumor cells express PD-L1, a protein that cancer cells use to hide from an immune system attack. But studies have demonstrated that PD-L1 expression status doesn’t neatly bucket responders and non-responders in the same way that testing for EGFR mutations or ALK rearrangements can, making it difficult for pharmaceutical companies to integrate PD-L1 testing for patient stratification in clinical trials.

In the absence of a universal diagnostic, Cancer Genetics is one lab that does offer all the FDA-approved companion and complementary PD-L1 tests, but also spends a lot of time educating doctors and pathologists on the differences between these tests and which to order for a particular immunotherapy. “There’s a big need for our pharma cousins to really push more knowledge about the associated diagnostics and tests and how to use them,” Sharma said. “That’s the only way they’re going to get uptake in the community setting.”

Despite the muddled messages around PD-L1 testing, healthcare providers and researchers nonetheless seem interested in PD-L1 testing as part of the tumor profiling workup for patients. Diaceutics’ surveys show a sharp uptick in the number of labs offering PD-L1 testing over the past year-and-a-half and 52 labs in the US offer at least one PD-L1 test. The company also reviewed biomarkers being studied in 95 Phase II/III NSCLC, and found that approximately half are incorporating patients’ PD-L1 status either alone or in combination with other markers, such as EGFR and ALK mutations.

At Cancer Genetics over the past year, there has also been a notable ramp up in orders for PD-L1 testing for lung cancer patients, but also for melanoma and head and neck cancer patients. “One our biggest volume increased tests this year has been PD-L1 testing,” Sharma said. “We think there is a lot of opportunity for significant additional growth.”

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.


Scientists think excessive population growth is a cause of scarcity and environmental degradation. A male pill could reduce the number of unintended pregnancies, which accounts for 40 percent of all pregnancies worldwide.


But, big drug companies long ago dropped out of the search for a male contraceptive pill which is able to chemically intercept millions of sperm before they reach a woman’s egg. Right now the chemical burden for contraception relies solely on the female. There’s not much activity in the male contraception field because an effective solution is available on the female side.


Presently, male contraception means a condom or a vasectomy. But researchers from Center for Drug Discovery at Baylor College of Medicine, USA are renewing the search for a better option—an easy-to-take pill that’s safe, fast-acting, and reversible.


The scientists began with lists of genes active in the testes for sperm production and motility and then created knockout mice that lack those genes. Using the gene-editing technology called CRISPR, in collaboration with Japanese scientists, they have so far made more than 75 of these “knockout” mice.


They allowed these mice to mate with normal (wild type) female mice, and if their female partners don’t get pregnant after three to six months, it means the gene might be a target for a contraceptive. Out of 2300 genes that are particularly active in the testes of mice, the researchers have identified 30 genes whose deletion makes the male infertile. Next the scientists are planning a novel screening approach to test whether any of about two billion chemicals can disable these genes in a test tube. Promising chemicals could then be fed to male mice to see if they cause infertility.


Female birth control pills use hormones to inhibit a woman’s ovaries from releasing eggs. But hormones have side effects like weight gain, mood changes, and headaches. A trial of one male contraceptive hormone was stopped early in 2011 after one participant committed suicide and others reported depression. Moreover, some drug candidates have made animals permanently sterile which is not the goal of the research. The challenge is to prevent sperm being made without permanently sterilizing the individual.


As a better way to test drugs, Scientists at University of Georgia, USA are investigating yet another high-tech approach. They are turning human skin cells into stem cells that look and act like the spermatogonial cells in the testes. Testing drugs on such cells might provide more accurate leads than tests on mice.


The male pill would also have to start working quickly, a lot sooner than the female pill, which takes about a week to function. Scientists from University of Dundee, U.K. admitted that there are lots of challenges. Because, a women’s ovary usually release one mature egg each month, while a man makes millions of sperm every day. So, the male pill has to be made 100 percent effective and act instantaneously.



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CHI’s Twelfth Annual Drug Discovery Chemistry Optimizing Small Molecules for Tomorrow’s Therapeutics April 23-27, 2017  |  San Diego, CA

Reporter: Aviva Lev-Ari, PhD, RN

Twelfth Annual

Drug Discovery Chemistry

Optimizing Small Molecules for Tomorrow’s Therapeutics

April 23-27, 2017  |  San Diego, CA


Save up to $200 —

Register by March 10

Hear Over 40 Presentations from Top Pharma Companies

Cambridge Healthtech Institute’s Twelfth Annual Drug Discovery Chemistry is a dynamic conference for medicinal chemists working in pharma and biotech. As in the past, participation by industry is once again very strong this year, with presentations from AbbVie, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, and Takeda. Preview more than 40 of these presentations below:


» Important Aspects of Fragment Screening Collection Design

Ashley Adams, Ph.D., Senior Scientist, Discovery Chemistry and Technology

» Comparison of Methods for Determination of Drug-Target Engagement in Live Cells

Aleksandra Baranczak, Ph.D., Senior Scientist, Discovery Chemistry and Technology

» Bruton’s Tyrosine Kinase (BTK) – Considerations for the Design and Profiling of Irreversible Covalent Inhibitors

Michael Friedman, Ph.D., Principal Scientist

» Targeting the PRC2 Complex through a Novel Protein-Protein Interaction Inhibitor of EED

Chaohong Sun, Ph.D., Senior Principal Research Scientist; Head, Fragment Based Drug Discovery, and Global Protein Sciences-Small Molecule

» Fragment-Based, Structure-Enabled Approach to the Discovery of Novel Inhibitors of the BET Family of Proteins: ABBV-075 and Others

Le Wang, Ph.D., Principal Research Scientist, Oncology Discovery, Chemistry

» Kinetic and Thermodynamic Profiling in Drug Discovery: Are We There Yet?

Ying Wang, Ph.D., Principal Research Scientist, Department of Chemistry and Technology


» Clinical Candidate AZD5153 Is a Novel Bivalent Inhibitor of BET Bromodomains

Huawei (Ray) Chen, Ph.D., Principal Scientist II, Oncology iMed

» Targeting Inducible Nitric Oxide Synthase (iNOS)

Fredrik Edfeldt, Ph.D., Associate Principal Scientist, Biophysics, Discovery Sciences


» Germinal-Center Kinase-Like Kinase Co-Crystal Structure Reveals a Swapped Activation Loop and C-Terminal Extension

Laura Silvian, Ph.D., Principal Scientist and Head, Physical Biochemistry

Boehringer Ingelheim

» Discovery of Novel Spiro[3H-Indole-3,2′-Pyrrolidin]-2(1H)-One Compounds as Chemically Stable and Orally Active Inhibitors of the MDM2–p53 Interaction

Andreas Gollner, Ph.D., Laboratory Head, Medicinal Chemistry

» Small Molecule Modulators of RORγ

Robert Hughes, Ph.D., Senior Associate Director, Small Molecule Discovery Research

» LTA4H Case Study: Parallel Core and Substituent FBDD to Clinical Compounds

Matthew R. Netherton, Ph.D., Senior Principal Scientist, Small Molecule Discovery Research, Medicinal Chemistry

Bristol-Myers Squibb

» Applications of the Thermal Shift Assay: More than Melts the Eye

Mary Harner, Ph.D., Research Investigator II, Leads Discovery & Optimization

» Compound Mechanism of Action: “The Known Unknown” and How That Affects Lead Optimization

Brian J. Murphy, Ph.D., Senior Principal Scientist, Fibrosis Drug Discovery, Disease Sciences and Biologics, R&D

» A Twisted Road to the Discovery of BMS-986142: Using Locked Atropisomers to Drive Potency in a Reversible Inhibitor of Bruton’s Tyrosine Kinase (BTK)

Joseph Tino, Ph.D., Senior Principal Scientist, Immunoscience Discovery Chemistry

» A First-in-Class Allosteric Inhibitor of TYK2 as a Potential Treatment for Inflammatory Autoimmune Diseases

Stephen Wrobleski, Principal Investigator, Immunoscience Chemistry


» Ligand-directed Degradation of GSPT1 by a Novel Cereblon Modulator

Philip Chamberlain, Ph.D., Principal Scientist, Biochemistry and Structural Biology

» Targeting Inducible Nitric Oxide Synthase (iNOS)

Fredrik Edfeldt, Ph.D., Associate Principal Scientist, Biophysics, Discovery Sciences

» Ozanimod: An S1P1,5R Modulator that Targets Lymphocyte Trafficking in Autoimmune and Inflammatory Disease

Kristin Taylor Meadows, Ph.D., Scientist III, Biology

Eli Lilly & Co

» Inhibiting Interaction of IL17A and Its Receptor

Sepideh Afshar, Ph.D., Principal Research Scientist, Department of Protein Engineering

EMD Serono

» Structure-Based Optimization of a Potent, Selective and CNS penetrable p70S6K/AKT Inhibitor M2698 for the Treatment of Tumors with PAM Pathway Genomic Alterations

Igor Mochalkin, Ph.D., Associate Director, Medicinal Chemistry & Lead Optimization


» The Development of Orally Bioavailable Antagonists of Inhibitor of Apoptosis Proteins (IAPs) for the Treatment of Cancer

Lewis Gazzard Ph.D., Senior Scientist, Discovery Chemistry

» Small Molecule Kinase Inhibitors for Brain Cancer: Limitations, Challenges and Opportunities

Timothy P. Heffron, Ph.D., Senior Scientist, Discovery Chemistry


» Affinity Selection Mass Spectrometry for Target Validation and Hit Triage

Jeff Messer, Director, NCE Molecular Discovery

» Using Encoded Library Technologies to Discover Small Molecule Inhibitors of RSV Protein Complexes

Christopher Phelps, Ph.D., Manager, Drug Design & Selection Boston, RD Platform Technology & Science


» Determination of a Focused Mini-Kinase Panel for Early Identification of Selective Kinase Inhibitors

Scott Bembenek, Ph.D., Principal Scientist, Computer-Aided Drug Discovery

» Discovery of a Series of Thiazole RORγt Inverse Agonists

Steven Goldberg, Ph.D., Associate Scientific Director, Immunology

» Combining Biophysical Techniques for Difficult Targets: Case Vignettes

Kevin Lumb, Ph.D., Scientific Director, Discovery Sciences

Merck & Co

» GPCR Structural Biology for Drug Discovery: Through the Protein Science Lens

Sujata Sharma, Ph.D., Director, Screening and Protein Science


» Design of Technology-Compatible Cyclic Peptide Scaffolds with Oral Bioavailability

Lauren Monovich, Ph.D., Senior Investigator, Global Discovery Chemistry

» Natural Products: Promising Starting Points for Fragment-Based Screening

Tim Schuhmann, Ph.D., Investigator III, Natural Products Unit

» Leniolisib (CDZ173) – The Discovery of a New Generation of Selective PI3Kδ Inhibitors

Nicolas Soldermann, Ph.D., Senior Investigator and Group Leader, Global Discovery Chemistry


» Inhibition of Autoimmune Pathways with Dual Inhibition of JAK1 and TYK2

Brian Gerstenberger, Ph.D., Principal Scientist, Medicinal Chemistry

» Advancing a Clinical Candidate Targeting IRAK4 from a Fragment Lead

Seungil Han, Ph.D., Associate Research Fellow, Structural Biology & Biophysics, WorldWide Research & Development

» Allosteric Activators of AMP-Activated Protein Kinase for the Treatment of Diabetic Nephropathy

Ravi G. Kurumbail, Ph.D., Research Fellow and Structural Biology Laboratory Head

» Macrocyclic Secondary Structure: Permeability and Chemical Biology

Spiros Liras, Ph.D., Vice President, Head, Cardiovascular Metabolism, RDRU and Discovery Network

» Discovery and Synthesis of the Macrocyclic EML4-ALK Inhibitor, Lorlatinib (PF-06463922)

Paul Richardson, Ph.D., Director, Process and Analytical Technologies, Oncology Medicinal Chemistry

» CASE STUDY: Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype Distinct Screening Hits

Mark E. Schnute, Ph.D., Medicine Design


» FBDD: Part of an Integrated Drug Discovery Platform

Derek Cole, Ph.D., Director, Medicinal Chemistry

» Discovery of NF-kappa-B-Inducing Kinase (NIK) Inhibitors

Walter Keung, Ph.D., Senior Scientist, Medicinal Chemistry

» Biophysical Characterization of GPCRs: SPR and Other Techniques

Phillip Schwartz, Ph.D., Senior Scientist, Biophysical Chemistry

» Fragments and SPR for GPCRs

Shuo Wang, Ph.D., Principal Scientist, Biophysical Chemistry

» Structure-Based Design, Synthesis, and Dermal Application of Novel Tyrosine Kinase 2 (TYK2) Inhibitors

Takatoshi Yogo, Ph.D., Principal Scientist, Research, Immunology Unit

Learn More | Present A Poster | Sponsor & Exhibit | Download Brochure


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Register by March 10




April 24-25

April 25-26

April 27

Inflammation Inhibitors

Kinase Inhibitor Chemistry

Biophysical Approaches

Protein-Protein Interactions, Part 1

Protein-Protein Interactions, Part 2

Small Molecules for Cancer Immunotherapy

GPCR-Targeted Drug Design

Fragment-Based Drug Discovery

Blood-Brain Penetrant Inhibitors

Macrocyclics & Constrained Peptides


From: Small Molecules <>

Date: Wednesday, February 15, 2017 at 11:11 AM

To: Aviva Lev-Ari <>

Subject: Hear 40+ Presentations from Top Pharma Companies at Drug Discovery Chemistry

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