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ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org Notre Dame: Drug Discovery Expertise and Resources Chemical Structure and Synthetic Methods Brandon Ashfeld (brain cancer) Paul Helquist (antibiotics, cancer, lysosomal storage disorders) Rich Taylor (cancer, Alzheimer’s disease) Biological Structure (Structure-based Design) Shahriar Mobashery (antibiotic resistance, cancer metastasis, stroke) Sergei Vakulenko (antibiotics) Olaf Wiest (epi-genetics, lysosomal storage disorders, antibiotics) Diagnostics and Delivery Bradley Smith (imaging and targeting agents, cancer, infectious disease) Marvin Miller (siderophore-antibiotic conjugates) Haifeng Gao (polymer-based nanostructures) Basar Bilgicer (ligand targeted liposomes) Pre-Clinical Studies Mayland Chang (antibiotics, stroke and traumatic brain injury)

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Notre Dame: Drug Discovery Expertise and Resources. Chemical Structure and Synthetic Methods Brandon Ashfeld (brain cancer) Paul Helquist (antibiotics, cancer, lysosomal storage disorders) Rich Taylor (cancer, Alzheimer’s disease) Biological Structure (Structure-based Design) - PowerPoint PPT Presentation

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Page 1: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

Notre Dame: Drug Discovery Expertise and Resources

Chemical Structure and Synthetic MethodsBrandon Ashfeld (brain cancer)Paul Helquist (antibiotics, cancer, lysosomal storage disorders)Rich Taylor (cancer, Alzheimer’s disease)

Biological Structure (Structure-based Design)Shahriar Mobashery (antibiotic resistance, cancer metastasis, stroke)Sergei Vakulenko (antibiotics)Olaf Wiest (epi-genetics, lysosomal storage disorders, antibiotics)

Diagnostics and DeliveryBradley Smith (imaging and targeting agents, cancer, infectious disease)Marvin Miller (siderophore-antibiotic conjugates)Haifeng Gao (polymer-based nanostructures)Basar Bilgicer (ligand targeted liposomes)

Pre-Clinical StudiesMayland Chang (antibiotics, stroke and traumatic brain injury)

Page 2: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

Notre Dame: Drug Discovery Expertise and Resources

Chemical Structure FacilitiesNuclear Magnetic Resonance, X-ray Crystallography, Mass Spec and ProteomicsChemical Synthesis and Drug Discovery FacilityComputer-Aided Molecular Design Facility

Biological FacilitiesGenomics and BioinformaticsMicroscopy and Flow CytometryIntegrated Imaging Facility

Institutes, Centers, and InitiativesHarper Cancer Institute (University of Notre Dame and IUSM-South Bend)Eck Institute for Global HealthCenter for Rare and Neglected DiseaseAdvanced Diagnostics & TherapeuticsAnalytical SciencesApplied and Computation Mathematics

Page 3: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

FDA Review/ Approval

FDA Review/ Approval

Clinical Trials Phase 0, I, II, III Clinical Trials

Phase 0, I, II, III Preclinical Studies

(Pharmacology & Tox.) Preclinical Studies

(Pharmacology & Tox.) Lead LeadHitHit

10,000 compounds10,000 compounds 250 compounds250 compounds 5 compounds5 compounds 1 compound1 compound

The number of FDA approved drugs decreased significantly between 1996 – 2010 despite more compounds prepared (combinatorial chemistry) and assayed (high throughput screening).

In addition to economic and bureaucratic factors, a likely scientific cause for this trend rests in the fact that the compounds produced and evaluated in large pharmaceutical compounds represent a small subset of chemical diversity space.

Page 4: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

Preclinical Studies (Pharmacology & Tox.)

Preclinical Studies (Pharmacology & Tox.) Lead LeadHitHit

10,000 compounds10,000 compounds 250 compounds250 compounds

The Warren Family Center for Drug Discovery

Facilitate Facilitate internal cross-disciplinary collaborations by internal cross-disciplinary collaborations by providing chemical synthesis and medicinal chemistry providing chemical synthesis and medicinal chemistry services.services.

Organize Organize the chemical products of past, the chemical products of past, current, and future chemical synthesis current, and future chemical synthesis and create the Notre Dame Chemical and create the Notre Dame Chemical Compound Collection.Compound Collection.

Promote external collaborations with regional screening centers at Purdue, Indiana University School of Medicine, and other academic facilities as well as Eli Lilly, BMS and other industrial partners.

Page 5: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

FDA Review/ Approval

FDA Review/ Approval

Clinical Trials Phase 0, I, II, III Clinical Trials

Phase 0, I, II, III Preclinical Studies

(Pharmacology & Tox.) Preclinical Studies

(Pharmacology & Tox.) Lead LeadHitHit

Page 6: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

FDA Review/ Approval

FDA Review/ Approval

Clinical Trials Phase 0, I, II, III Clinical Trials

Phase 0, I, II, III Preclinical Studies

(Pharmacology & Tox.) Preclinical Studies

(Pharmacology & Tox.) Lead LeadHitHit

CTSA

Page 7: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

The Indiana Drug Discovery Alliance (IDDA)

The Molecular Therapeutics program within the Indiana CTSI is pleased to announce the creation of the Indiana Drug Discovery Alliance. The IDDA’s objective is to promote and support promising early stage drug discovery research. The IDDA will facilitate collaborative translational research and partnerships through identification of complementary expertise across and support for team building across diverse disciplines. The IDDA will be a clearinghouse for drug discovery and development resources available through Indiana-CTSI colleagues and, when necessary, identify and fill gaps through the new, external partnerships. The IDDA will seek to expand our current capabilities and knowledge base by providing access to education resources to faculty and students on translational drug discovery.

Page 8: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

The Indiana Drug Discovery Alliance (IDDA) Internal Advisory Committee

Yvonne Lai – Senior Scientist, Department of Psychology and Brain Sciences, Indiana University-Bloomington

Jay McGill – Senior Director, Eli Lilly and Company and Translational Science Officer, Biocrossroads

Andrew Mesecar – Walther Professor of Cancer Structural Biology; Purdue University

Tim Ratliff – Professor of Comparative Pathobiology and Director of the Center for Cancer Research; Purdue University

Scott Sheehan - Senior Director Molecular Design and Lead Generation Technologies, Eli Lilly and Company

Richard Taylor – Professor of Chemistry and Biochemistry, Interim Director Warren Family Center for Drug Discovery and Associate Vice President for Research; University of Notre Dame

Michael VanNieuwenhze – Associate Professor, Department of Chemistry, Indiana University-Bloomington

Zhong-Yin Zhang – Harris Professor and Chairman, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine

Page 9: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

Call for Proposals

PROPOSAL DEADLINE; July 1, 2014

The IDDA has created a competitive program that will provide funds and/or consultation to support early stage development of therapeutics. Small grants will be available to support new collaborations and/or the use of core facilities that enable the translation of fundamental discoveries related to drug discovery. Critical research proposal feedback will be provided from the team of experienced industry and academic experts within our internal advisory committee as well as through ad hoc, project-specific pharmaceutical expert reviewers. Funded projects will be developed in consultation with the internal advisory committee.

Page 10: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

Call for Proposals

The IDDA currently seeks proposals through three classifications:

Type 1: Chemical Lead Development: Projects with unique chemical entities seeking in vitro or in vivo biological screening and evaluation, molecular target identification, computational design and medicinal chemistry services, and/or early stage preclinical evaluation.

Type 2: Biological Target Validation: Projects with fundamental biological targets seeking assay development, in silico screening, high-throughput screening, hit identification, chemical synthesis and/or medicinal chemistry services.

Type 3:  Molecular Design and Library Development: Projects seeking to utilize computational and medicinal chemistry core facilities for design and synthesis of small molecules for placement in the CTSI chemical compound collection.

Page 11: Notre Dame: Drug Discovery Expertise and Resources

ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH

www.indianactsi.org

 GENERAL GUIDELINES

1.Applicants must be full-time researchers (tenure, tenure-track, or research faculty) within the Indiana-CTSI.2.Funds are available up to $15,000 but budget and budget justification are not required at this stage. Final budgets will be developed in consultation with the internal advisory committee.3.The proposal should be single-spaced and a maximum of two pages in length (Arial, 11pt) with no less than 0.5 inch margins. 4.The proposal should be submitted through the CTSI Hub as a single PDF document with naming convention, “principal investigator_IDDA_type#.pdf”. The following must be included within the two-page limit:1.Name, title and affiliation of applicant and co-investigators.2.A brief background describing the drug discovery-related project emphasizing therapeutic relevance and significance.3.Current status of project.4.NIH-style, 4-page biosketches for the PI and co-investigators should be included as an appendix.