Notre Dame: Drug Discovery Expertise and Resources
Chemical Structure and Synthetic Methods
Brandon Ashfeld (brain cancer)
Paul Helquist
Rich Taylor
(antibiotics, cancer, lysosomal storage disorders)
(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
Haifeng Gao
Basar Bilgicer
(siderophore-antibiotic conjugates)
(polymer-based nanostructures)
(ligand targeted liposomes)
Pre-Clinical Studies
Mayland Chang (antibiotics, stroke and traumatic brain injury)
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

Notre Dame: Drug Discovery Expertise and Resources
Chemical Structure Facilities
Nuclear Magnetic Resonance, X-ray Crystallography, Mass Spec and Proteomics
Chemical Synthesis and Drug Discovery Facility
Computer-Aided Molecular Design Facility
Biological Facilities
Genomics and Bioinformatics
Microscopy and Flow Cytometry
Integrated Imaging Facility
Institutes, Centers, and Initiatives
Harper Cancer Institute (University of Notre Dame and IUSM-South Bend)
Eck Institute for Global Health
Center for Rare and Neglected Disease
Advanced Diagnostics & Therapeutics
Analytical Sciences
Applied and Computation Mathematics
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

The number of FDA approved drugs decreased significantly between 1996 – 2010 despite more compounds prepared (combinatorial chemistry) and assayed (high throughput screening).
Hit Lead
Preclinical Studies
(Pharmacology & Tox.)
Clinical Trials
Phase 0, I, II, III
FDA Review/
Approval
10,000 compounds 250 compounds 5 compounds 1 compound
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 .
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

Hit Lead
Facilitate internal cross-disciplinary collaborations by providing chemical synthesis and medicinal chemistry services.
Preclinical Studies
(Pharmacology & Tox.)
10,000 compounds 250 compounds
Organize the chemical products of past, current, and future chemical synthesis and create the Notre Dame Chemical
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.
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

Hit Lead
Preclinical Studies
(Pharmacology & Tox.)
Clinical Trials
Phase 0, I, II, III
FDA Review/
Approval
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

Hit Lead
Preclinical Studies
(Pharmacology & Tox.)
Clinical Trials
Phase 0, I, II, III
FDA Review/
Approval
C
T
S
A
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

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 .
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
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

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.
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org

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.
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.
ACCELERATING CLINICAL AND TRANSLATIONAL RESEARCH www.indianactsi.org