DRUG DESIGN & DISCOVERY IN ACADEMIA Vladimir Poroikov ...Cost: 0.8 – 3.0 mln USD. Outlook 1. General info 1.1. Terminology 1.2. Needs of the Society for new medicines 1.3. Criticism

DRUG DESIGN & DISCOVERY IN ACADEMIA

Vladimir Poroikov, Prof. Dr.

Orekhovich Institute of Biomedical Chemistry of Rus. Acad. Med. Sci., Pogodinskaya Str. 10/8, Moscow, 119121, Russia

http://www.ibmc.msk.ru

Kazan Summer School on Chemoinformatics Kazan - August 26-29, 2013

Outlook 1. General info 1.1. Terminology 1.2. Needs of the Society for new medicines 1.3. Criticism and challenges of pharmaceutical industry 1.4. Advantages & disadvantages of drug discovery in academy 1.5. NIH Road Map initiative and screening centers 1.5. Particular problems in this field in Russia and

possible solutions 2. Examples of drug design & discovery in academy 2.1. Some new medicines discovered by academy 2.2. CADD software and databases vendors 2.3. Web-services for CADD

2.4. Our own experience in the field of drug discovery 3. Summary

Let us talk a little bit about the terms

University

Russian Academy of Sciences Russian Academy of Medical Sciences

Jenwitheesuk et al. Trends in Pharmacol. Sci., 2008, 62-71.

More Introduction on the Terminology Drug: a compound with Food and Drug Administration (FDA) approval for human use. Drug-like compound: a compound (including research and experimental drugs) that has been shown to have physiological activity in at least nonhuman in vivo systems. Hit: a compound that inhibits (or has high binding affinity for) one or more targets. In our case, the hits are initially virtual – that is, computationally derived. Lead: a hit that has been well-characterized experimentally. For example, one that has been shown to have a high dissociation constant (Kd) for the target of interest such that the functional activities of the target are decreased on binding and/or has demonstrated effectiveness of treatment against disease in an animal model. Potential lead: a computationally predicted hit that has been shown to work experimentally against in vitro (cell culture) disease models of the organism.


possible solutions 2. Examples of drug design & discovery in academy 2.1. Some new medicines discovered by academy 2.2. CADD software and databases vendors 2.3. Web-services for CADD 2.4. Our own experience in this field

3. Conclusions

The Mission:

Better Medicines through Global Education and Research

The International Union of Basic and Clinical Pharmacology

http://www.iuphar.org/

The Need of the Society to Get More Safety and Potent Drugs:

No efficient drugs for many diseases;

Severe adverse effects of many drugs;

Emerging resistance.

Current R & D Process of New Pharmaceuticals

Cost: 0.8 – 3.0 mln USD.




Current Criticism and Challenges of Pharma Industry

Reduced Efficiency Declining Innovation Key Patent Expirations Fierce Price Competition From Generics High Regulatory Hurdles Tarnished Image

Abou-Gharbia & Childers, J. Med. Chem., April 4, 2013.

PHRMA: Pharmaceutical Industry Profile 2009 (www.pharma.org).

Gap in Pharmaceutical Industry Between the R & D Spending and Number of NCEs Approved




Frearson J. and Wyatt P. Expert Opin. Drug Discov., 2010, 5: 909-919.

Where Academy Can Make a Visible Impact in Drug Discovery:

Partially de-risking novel drug discovery targets;

Neglected and orphan diseases;

New paradigms for drug discovery;

Training young scientists in the practice of drug discovery and

educating basic scientists in translational research.

Broad Expertise Within Universities Promotes Multidisciplinary Studies

To develop new methods and approaches in areas such as:

Data mining;

Informatics;

Computational chemistry;

Compound library selection and design;

Synthetic organic chemistry methodology;

Parallel synthetic and purification technology;

In silico pharmacokinetics and toxicity predictions;

Animal models for efficacy and toxicity.


Translational Opportunities from Universities (1970-1980)

Early licensing to, or partnering with, the pharma or biotech

companies;

Spin-offs (most floundered and did not deliver sustainable

companies, there have been significant exceptions such as

Genentech).

Some Examples of Academic Drug Discovery Centers University of Florida, Center for Drug Discovery URL: http://www.cop.ufl.edu/centers/cdd/index.htm Computational design, chemistry, PK and PD

Centre for Integrative Chemical Biology and Drug Discovery, University of North Carolina, USA URL: http://pharmacy.unc.edu/labs/center-for-integrative-chemical-biology-and-drug-discovery HTS and medicinal chemistry aimed at development of leads and probe compounds to support target validation

University of Dundee--Drug Discovery Unit, Dundee, UK URL: http://www.drugdiscovery.dundee.ac.uk/ Translational drug discovery for unmet medical needs and neglected diseases Focus: Tropical diseases; novel targets and mechanisms; stem cells University of Leuven--Centre for Drug Design and Discovery, Leuven, Belgium URL: http://lrd.kuleuven.be/en/entrepreneur/collaboration/cd3/about.htm To collaborate with academic research groups and small companies on innovative targets or approaches (Viral, bacterial, fungal diseases; CNS disorders; cancer)


Pro’s & Contra’s for Academic Drug Discovery

Coupling of academic minds with experienced drug discovery scientists resulting in enormously potent teams.

Populating these groups with a mixture of PhD students and post-doctorates.

Need to shift priorities and work flows and to close non-progressing projects.

Need to have coherent PhD thesis projects and for post-doctorates to publish.

Lack of experience of PhD and post-doctorates does not match the usual rapid progress required by funders to address the aggressive timelines set.





Molecular Libraries Initiative

Molecular Libraries Probe Production Centers Network




Basic Research

Translational Research

Applied Research

Cost

Risks

Adopted from the presentation of Eli Lilly Vice-President Andrew Dahlem at the American-Russian Scientific Forum (Moscow, Russia, November 16-18, 2011).

Who Is Paying for What?

Budget

Market

A Gap Between the Academic Studies and Pharma Development

Adopted from the presentation of Andrey Ivashchenko (ChemRar), 2007.

http://pharma2020.ru

Partially This Gap Can Be Overcame Due to the “Pharma-2020” Research Program

Another Source of Funds in This Field Is Biomedical Cluster of Skolkovo

http://community.sk.ru/

Федеральный закон Российской Федерации от 2 августа 2009 г. N 217-ФЗ "О внесении изменений в отдельные законодательные акты Российской Федерации по вопросам

создания бюджетными научными и образовательными учреждениями хозяйственных обществ в целях практического применения (внедрения) результатов

интеллектуальной деятельности"

31. Бюджетные научные учреждения и созданные государственными академиями наук научные учреждения имеют право без согласия собственника их имущества с уведомлением федерального органа исполнительной власти, осуществляющего функции по выработке государственной политики и нормативно-правовому регулированию в сфере научной и научно-технической деятельности, быть учредителями (в том числе совместно с другими лицами) хозяйственных обществ, деятельность которых заключается в практическом применении (внедрении) результатов интеллектуальной деятельности (программ для электронных вычислительных машин, баз данных, изобретений, полезных моделей, промышленных образцов, селекционных достижений, топологий интегральных микросхем, секретов производства (ноу-хау), исключительные права на которые принадлежат данным научным учреждениям. При этом уведомление о создании хозяйственного общества должно быть направлено бюджетным научным учреждением или созданным государственной академией наук научным учреждением в течение семи дней с момента внесения в единый государственный реестр юридических лиц записи о государственной регистрации хозяйственного общества. Денежные средства, оборудование и иное имущество, находящиеся в оперативном управлении бюджетного научного учреждения или созданного государственной академией наук научного учреждения, могут быть внесены в качестве вклада в уставный капитал создаваемого хозяйственного общества в порядке, установленном Гражданским кодексом Российской Федерации.

Birch Bayh Bob Joseph Dole The Bayh–Dole Act or Patent and Trademark Law Amendments Act is United States legislation dealing with intellectual property arising from federal government-funded research. Sponsored by two senators, Birch Bayh of Indiana and Bob Dole of Kansas, the Act was adopted in 1980, is codified in 35 U.S.C. § 200-212, and is implemented by 37 C.F.R. 401.

Why Academic Research Are Easily Translated to Practice in the US?

Recent News from the Russian President

. . .

Aims and Functions of a New Foundation

Is It an Analog of the Bayh–Dole Act?




Contribution of Publicly Funded Research to Creating New Drugs

Studies have estimated the contribution of publicly funded

research to the delivery of FDA approved medicines, both

molecular and biological entities, to be from between 16 and 50%.


Examples of Launched Pharmaceuticals Originated from Universities

Димебон – новый перспективный препарат для лечения нейродегенеративных заболеваний

Сентябрь 03 , 2008

Pfizer и Medivation опубликовали соглашение о совместной коммерциализации димебона. Medivation получает $225 миллионов предоплаты и по выполнению следующего пункта $ 500 миллионов и еще дополнительно по закрытому соглашению.

Medivation receive US $ 725 M

Cентябрь 03, 2008

Медивейшн получила разрешение FDA начать испытания димебона против болезни Хантингтона

Zefirov N.S., Man and Drugs, 2013

Latrepirdine hydrochloride is an antihistamine launched by the Russian Academy of Sciences for the treatment of skin allergy and allergic rhinitis. In May 2010, Medivation and Pfizer announced that phase III evaluation of latrepirdine for the treatment of moderate to severe Alzheimer's disease (AD) was being halted due to lack of efficacy. This decision did not affect ongoing studies in patients with mild to moderate AD, however no recent development has been reported for this research. In 2011, the companies discontinued phase III clinical studies for the treatment of Huntington's disease based on phase III trial data which did not achieve statistical significance for either of the coprimary endpoints. In addition to its antihistaminic properties, the compound has recently been shown to bind to cholinesterase and the NMDA receptor, the two validated targets for the treatment of Alzheimer's disease. Latrepirdine has been shown to improve learning and memory in animal models of Alzheimer's disease and in an open-label 14-patient pilot clinical study in Alzheimer's disease patients. In 2008, the compound was licensed to Merck Serono for the treatment of Alzheimer's type dementia and for the treatment of Huntington's disease.

Studies on Possible New Use of Dimebon

Further Studies of Dimebon and Its Analogs

. . .

InterLek Is a Resident of “Skolkovo” Now

Chemical Libraries and Custom Synthesis Providers




http://www.tripos.com/

Well-Known CADD Software Company Originated from University

http://www.netsci.org/Science/Compchem/feature17a.html

“A Scrolling History of Computational Chemistry”

http://algodign.com

Example of US-Russian Company Aimed to Development of New SBDD Methods

http://www.srcc.msu.su/nivc/about/lab/lab1_5.html

One Group from Former Algodign (Dr. Vladimir Sulimov and Associates)

http://lenmp.sinp.msu.ru/laboratory.html

Another Group from Former Algodign (Dr. Eugene Tkalya and Associates)

http://q-pharm.com/

http://infochim.u-strasbg.fr/recherche/isida/index.php

http://www.moltech.ru/




http://www.vcclab.org/

https://ochem.eu/home/show.do

http://chembench.mml.unc.edu/

It Was One of the First Freely-Available Web-Services on Biological Activity Prediction

Total users: 8890 Total prediction: 305730 Total countries: 91

http://www.way2drug.com/passonline

France - 2741 Mexico - 5465 Australia - 7043

Other countries 24585

Italy - 8718

Ukrane - 10948

Kazakhstan - 11733

Poland - 13950

Chine - 14495

India - 59564 USA - 9552

Russia - 136935

Russia 136935 India 59564 China 14495 Poland 13950 Kazakhstan 11733 Ukraine 10948 USA 9552 Italy 8718 … …

Country Predictions

Publicly available resources (PubChem, ChEMBL, DrugBank etc.), which contain data about biological activities of substances, became the bases for development of several computer programs predicting biological activity of chemical compounds.

Recently Appeared Open Data Resources

http://www.chemspider.com/

ChemSpider Website

SuperPred Website

http://bioinformatics.charite.de/superpred/

CPI-DRAR Website

http://cpi.bio-x.cn/drar/

SEA Website

http://sea.bkslab.org/

Evaluation Set on Pharmaceuticals Approved by US FDA in 2011

- 6 biopreparations

- 24 synthetic drug-like substances

(New Chemical Entities)

Excluded:

Gadobutrol is the BBB imaging gadolinium-based contrast agent

Ioflupane is iodine isotope I123

Chemical classes of 22 medicines

Androstanes Pyridines

Antibiotic macrolide Pyrrolopyridines

Benzimidazoles Pyrrolopyrimidines

Benzodiazepines Quinazolines

Benzofurans Quinolines

Cyclopentapyrroles Substituted benzonitriles

Fluorobenzylamines Substituted cyclohexaneacetic acid Oxazolidinones

Peptides Tetraazacyclododecanes

Purines Triazolopyrimidines

Medicines, Pharmacological Effects, Mechanisms of Action

Generic Name (trade name) Indication Properties

Abiraterone (Zytiga) Metastatic castration-resistant prostate cancer CYP17 inhibitor

Azilsartan (Edarbi) Hypertension Angiotensin II type 1 receptor Antagonist

Boceprevir (Victrelis) HCV genotype 1 NS3/4A protease inhibitor

Clobazam (Onfi) Seizures associated with Lennox–Gastaut syndrome Benzodiazepine

Crizotinib (Xalkori) ALK-positive advanced or metastatic NSCLC ALK inhibitor

Deferiprone (Ferriprox) Transfusional iron overload due to thalassaemia syndromes Iron chelator

Ezogabine (Potiga) Partial-onset seizures Potassium channel opener Fidaxomicin (Dificid) Clostridium difficile-associated diarrhoea RNA polymerase inhibitor

Gabapentin enacarbil (Horizant) Moderate-to-severe restless legs syndrome Voltage-activated calcium channel Inhibitor

Icatibant (Firazyr) Hereditary angioedema Bradykinin B2 receptor antagonist

Indacaterol (Arcapta neohaler) COPD Long-acting β2-adrenergic receptor agonist

Linagliptin (Tradjenta) Type 2 diabetes Dipeptidyl peptidase 4 inhibitor

Rilpivirine (Edurant) HIV-1 infection Non-nucleoside reverse transcriptase inhibitor

Rivaroxaban (Xarelto) Prophylaxis of deep vein thrombosis in hip and knee replacement surgery Factor Xa inhibitor

Roflumilast (Daliresp) COPD exacerbations Phosphodiesterase 4 inhibitor Ruxolitinib (Jakafi) Intermediate or high-risk myelofibrosis JAK1/JAK2 inhibitor Spinosad (Natroba) Head lice Causes neuronal excitation in insects Telaprevir (Incivek) HCV genotype 1 NS3/4A protease inhibitor

Ticagrelor (Brilinta) Thrombotic cardiovascular events in patients with acute coronary syndrome P2Y12 platelet inhibitor

Vandetanib (Caprelsa) Unresectable or metastatic medullary thyroid cancer VEGF, EGFR and RET inhibitor

Vemurafenib (Zelboraf) BRAF-positive unresectable or metastatic melanoma BRAF inhibitor

Vilazodone (Viibryd) Major depressive disorder Selective serotonin reuptake inhibitor and 5‑HT1A partial agonist

Test set compounds are described by only one main

pharmacological indication and mechanism of action.

For drugs, usually, about twenty different pharmacological

effects, mechanisms of action, toxic and adverse effects, and

other biological activities are known.

So, the only real possibility in this study is to apply as a

criteria:

Sensitivity = «Predicted»/«Known Activities»

Validation method

Validation results

Generic Name (trade name) ChemSpider SuperPred CPI-DRAR SEA PASS Online Eff. M. Eff. M. Eff. M. Eff. M. Eff. M.

Abiraterone (Zytiga) Azilsartan (Edarbi) Boceprevir (Victrelis) Clobazam (Onfi) Crizotinib (Xalkori) Deferiprone (Ferriprox) Ezogabine (Potiga) Fidaxomicin (Dificid) Gabapentin enacarbil (Horizant) Icatibant (Firazyr) Indacaterol (Arcapta neohaler) Linagliptin (Tradjenta) Rilpivirine (Edurant) Rivaroxaban (Xarelto) Roflumilast (Daliresp) Ruxolitinib (Jakafi) Spinosad (Natroba) Telaprevir (Incivek) Ticagrelor (Brilinta) Vandetanib (Caprelsa) Vemurafenib (Zelboraf) Vilazodone (Viibryd) 3 7 12 4 16 18 20 16

Comparison of Web-services

Web-service Input Data Sensitivity Time cost

ChemSpider (LASSO) MOL 0.136 <10 minutes

SuperPred MOL 0.318 <10 minutes

CPI-DRAR MOL2 0.364 >500 hours

SEA SMILES 0.773 >120 hours*

PASS Online MOL 0.818 <10 minutes

*Effective time

Comparison of Web-services

ChemSpider 3

SuperPred 7

CPI-DRAR 16

SEA 34 PASS Online

36

1 1

3 6

6

2

Over fifty publications with independent confirmation of PASS online predictions

Ajay Kumar, Poonam Lohan, Deepak K. Aneja, Girish Kumar Gupta, Dhirender Kaushik, Om Prakash. (2012). Design, synthesis, computational and biological evaluation of some new hydrazino derivatives of DHA and pyranopyrazoles. European Journal of Medicinal Chemistry, 50: 81-89. Azza A. Kamel, Athina Geronikaki, Wafaa M. Abdou. (2012). Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation. European Journal of Medicinal Chemistry, 51: 239-249. Chandrika B-Rao et al. (2012). Identification of novel isocytosine derivatives as xanthine oxidase inhibitors from a set of virtual screening hits. Bioorganic & Medicinal Chemistry, 20: 2930–2939. Donatella Verbanac, Subhash C. Jain, Nidhi Jain, Mahesh Chand, Hana Cipcic Paljetak, Mario Matijasic, Mihaela Peric, Visnja Stepanic, Luciano Saso. (2012). An efficient and convenient microwave-assisted chemical synthesis of (thio)xanthones with additional in vitro and in silico characterization. Bioorganic & Medicinal Chemistry, 20: 3180–3185. Wafaa M. Abdou, Azza A. Kamel, Rizk E. Khidre, Athina Geronikaki, and Maria T. Ekonomopoulou. (2012). Synthesis of 5- and 6-N-heterocyclic Methylenebisphosphonate Derivatives and Evaluation of their Cytogenetic Activity in Normal Human Lymphocyte Cultures. Chem. Biol. Drug. Des., 79: 719–730. Navarrete-Vazquez G., Hidalgo-Figueroa S., Torres-Piedra M., et al. (2010). Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivatives. Bioorganic & Medicinal Chemistry, 18 (11): 3985–3991. Mustafayeva K., Di Giorgio C., Elias R., et al. (2010). DNA-Damaging, mutagenic, and clastogenic activities of gentiopicroside isolated from Cephalaria kotschyi roots. Journal of Natural Products, 73 (2): 99–103. Raja A.K., Vimalanathan A.B., Raj S.V., et al. (2010). Indispensable chemical genomic approaches in novel systemic targeted drug discovery. Biology and Medicine, 2 (3): 26-37. Torres-Piedra M., Ortiz-Andrade R., Villalobos-Molina R., et al. (2010). A comparative study of flavonoid analogues on streptozotocinenicotinamide induced diabetic rats: Quercetin as a potential antidiabetic agent acting via 11b–Hydroxysteroid dehydrogenase type 1 inhibition. European Journal of Medicinal Chemistry, 45: 2606-2612. Benchabane Y., Di Giorgio C., Boyer G., et al. (2009). Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine. European Journal of Medicinal Chemistry, 44: 2459–2467. Hernandez-Nunez E., Tlahuext H., Moo-Puc R., et al. (2009). Synthesis and in vitro trichomonicidal, giardicidal and amebicidal activity of N-acetamide(sulfonamide)-2-methyl-4-nitro-1H-imidazoles. European Journal of Medicinal Chemistry, 44 (7), 2975-2984. Babaev E.V. (2009). Combinatorial chemistry at the university: ten years experience of research, educational and organizational projects. Russsian Chemical Journal, 53 (5), 140-152. Ghadimi S., Ebrahimi-Valmoozi A.A. (2009). Lipophilicity, electronic, steric and topological effects of some phosphoramidates on acethylcholinesterase inhibitory property. J. Iran. Chem. Soc., 6 (4): 838-848.

. . .

GUSAR: General Unrestricted Structure-Activity Relationships

Filimonov D.A. et al. SAR and QSAR Environ. Res., 2009, 20: 679.

-0.10 -0.05 0.00 0.05 0.10 0.15 0.20

2D Cerius2

3D Cerius2

CoMSIA

EVA

CoMFA

HQSAR

GFA

MLR

PLS

delta R2 test

delta Q2

delta R2

C1 O

2

O3

H4

H 5

0 1 1 1 0 1 0 0 0 1 C = 1 0 0 0 0 1 0 0 0 0 0 1 0 0 0

1.40 -0.59 -0.57 -0.57 0.14 -0.59 1.27 0.14 0.14 -0.54

( )C21Exp − = -0.57 0.14 1.13 0.13 -0.02

-0.57 0.14 0.13 1.13 -0.02 0.14 -0.54 -0.02 -0.02 1.13

a) b) c)

EA IP A B P Q C 1.263 11.26 6.262 0.316 -0.00218 -0.1820 O 1.461 13.62 7.541 0.287 0.02944 0.3019 O 1.461 13.62 7.541 0.287 0.06199 0.5297 H 0.754 13.60 7.177 0.279 0.05812 0.4706 H 0.754 13.60 7.177 0.279 0.05304 0.3533

d)

http://way2drug.com/gusar

GUSAR-Based Web-Services

Zakharov A. et al. Chem.Res.Toxicol, 2012, 25: 2378-2385. Lagunin A. et al. Mol. Informatics, 2011, 30: 241–250.

Just Created Web-Service for Predicting Expression Profiles

http://way2drug.com/GE

http://www.way2drug.com

Link to the Future Integration of Our Web-Services

Outlook 1. General info 1.1. Terminology 1.2. Needs of the Society for new medicines 1.3. Criticism and challenges of pharmaceutical industry 1.4. Advantages & disadvantages of drug discovery in academy 1.5. NIH Road Map initiative and screening centers 1.5. Particular problems in this field in Russia and possible

solutions 2. Examples of drug design & discovery in academy 2.1. Some new medicines discovered by academy 2.2. CADD software and databases vendors 2.3. Web-services for CADD 2.4. Our own experience in the field of drug discovery

3. Conclusions

Drug repositioning: new indications for known drugs

Discovery of nootropic effect of some antihypertensive drugs

0102030405060708090

Pa (N

ootr

opic

Effe

ct)

PASS Predictions Patrolling Behavior of Mice

in Cross-Maize Results

Perindopril in dose of 1 mg/kg, and quinapril and monopril in doses of 10 mg/kg improved the patrolling behavior in the maize, similar to the effects of piracetam and meclofenoxate (in doses of 300 and 120 mg/kg, respectively). The observed nootropic effect of these ACE inhibitors is likely to be unrelated to their

antihypertensive effect, since the nootropic action took place only at relatively low doses of perindopril, quinapril and monopril and was not observed with further increase in dose.

Kryzhanovskii S.A. et al. Pharmaceutical Chemistry Journal, 2012, 45: 605-611.

«Патентовать нельзя публиковать»

Paper was prepared in 2005, and put in a desk drawer. We were waiting for a patenting: 2005,

2011 . . . 2006, 2007, 2008, 2009, 2010,

The Paper Has Been Published Only in 2012

Participants: 9 teams from 8 countries

European project «From analysis of gene regulatory networks to drug» (Net2Drug)

ChemNavigator database (~24,000,000 structures of organic

compounds)

Virtual screening of potential multitarget anticancer substances (PASS, GUSAR)

11 compounds tested in cellular assays

2 active compounds (BC, melanoma)

Synergism with RITA.

Activity confirmed in experiments on mouse xenograft models

ALab – resident of «Skolkovo» (2012)

Grant of«Skolkovo» (2013)

Further progress:

A-Laboratory as a Resident of Skolkovo

http://genexplain.com

New German Company That Integrates Chemo- and Bioinformatics

http://genexplain.com

This Company Is also Doing Marketing of our CADD Products




Summary Academy contributes to many fields of drug design and discovery,

including:

Data mining;

Informatics;

Computational chemistry;

Compound library selection and design;

Synthetic organic chemistry methodology;

Parallel synthetic and purification technology;

In silico pharmacokinetics and toxicity predictions;

Animal models for efficacy and toxicity.

Acknowledgements IBMC Dmitry Filimonov, Ph.D. Alexey Lagunin, Ph.D. Tatyana Gloriozova Anastasia Rudik, Ph.D. Olga Tarasova (Filz), Ph.D. Sergey Ivanov, Ph.D. Student Pavel Pogodin, Student

NCI/NIH, Frederick, MD Marc Nicklaus, Ph.D. Alexey Zakharov, Ph.D. Laura Guasch, Ph.D. Stephen Hughes, Ph.D. Steven Smith, Ph.D.

Funding: RFBR (03-07-90282, 05-07-90123, 06-03-08077), CRDF (RC1-2064), INTAS (00-0711, 03-55-5218), ISTC (3197, 3777), FP6 (LSHB-CT-2007-037590), FP7 (200787), RFBR/CRDF grant # 12-04-91445-NIH_А/RUB1-31081-MO-12, SKOLKOVO Foundation.

Karolinska Institute, Stockholm, Sweden Galina Selivanova

GeneXplain GMbH, Wolfenbuettel, Germany Alexander Kel, Edgar Wingender

Annual Symposium on Bioinformatics and Computer-Aided Drug Discovery in the Framework of Russian

National Congress “Man and Drugs”

20th EuroQSAR Understanding Chemical-Biological Interactions

Documents

DRUG DESIGN & DISCOVERY IN ACADEMIA Vladimir Poroikov ...Cost: 0.8 – 3.0 mln USD. Outlook 1. General info 1.1. Terminology 1.2. Needs of the Society for new medicines 1.3. Criticism