SCOTT D. LARSEN, Ph.D. PROFESSIONAL EXPERIENCE University of Michigan, Ann Arbor, MI Joseph Burckhalter Collegiate Research Professor 2014 - present Director of Vahlteich Medicinal Chemistry Core 2012 - present Research Professor of Medicinal Chemistry – College of Pharmacy 2007 - present Co-Director of Vahlteich Medicinal Chemistry Core 2007 - 2012 Pfizer, Inc., Ann Arbor, MI Research Fellow – Cardiovascular Chemistry 2003 - 2007 Group leader (4-8 PhD and BS/MS chemists) Pharmacia / Pharmacia & Upjohn / The Upjohn Co., Kalamazoo, MI Associate Director and Fellow – Medicinal Chemistry 2002 - 2003 Management of 5 PhD and 8 BS/MS chemists Senior Research Advisor – Medicinal Chemistry 2001 - 2002 Senior Scientist – Combinatorial and Medicinal Chemistry 1997 - 2001 Senior Research Scientist – Medicinal Chemistry 1992 - 1997 Research Scientist – Metabolic Diseases 1988 - 1992 Scientist – Atherosclerosis and Thrombosis 1985 - 1988 EDUCATION Postdoctoral Research, Indiana University 1984-1985 Advisor: Paul Grieco Development of novel iminium Diels-Alder cycloadditions Ph.D. Organic Chemistry, University of Wisconsin-Madison 1983 Thesis Advisor: Edwin Vedejs Thesis Title: Macrocyclic Pyrrolizidine Alkaloids: The Total Synthesis of d,l-Fulvine and d,l-Crispatine
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SCOTT D. LARSEN, Ph.D.
PROFESSIONAL EXPERIENCE
University of Michigan, Ann Arbor, MIJoseph Burckhalter Collegiate Research Professor 2014 - presentDirector of Vahlteich Medicinal Chemistry Core 2012 - present Research Professor of Medicinal Chemistry – College of Pharmacy 2007 - presentCo-Director of Vahlteich Medicinal Chemistry Core 2007 - 2012
Pfizer, Inc., Ann Arbor, MI Research Fellow – Cardiovascular Chemistry 2003 - 2007
Group leader (4-8 PhD and BS/MS chemists)
Pharmacia / Pharmacia & Upjohn / The Upjohn Co., Kalamazoo, MIAssociate Director and Fellow – Medicinal Chemistry 2002 - 2003
Management of 5 PhD and 8 BS/MS chemistsSenior Research Advisor – Medicinal Chemistry 2001 - 2002Senior Scientist – Combinatorial and Medicinal Chemistry 1997 - 2001Senior Research Scientist – Medicinal Chemistry 1992 - 1997Research Scientist – Metabolic Diseases 1988 - 1992Scientist – Atherosclerosis and Thrombosis 1985 - 1988
EDUCATION
Postdoctoral Research, Indiana University 1984-1985Advisor: Paul GriecoDevelopment of novel iminium Diels-Alder cycloadditions
Ph.D. Organic Chemistry, University of Wisconsin-Madison 1983Thesis Advisor: Edwin VedejsThesis Title: Macrocyclic Pyrrolizidine Alkaloids: The Total Synthesis of d,l-Fulvine and d,l-Crispatine
B.S. Chemistry (summa cum laude), Alma College, Alma, MI 1979
HONORS AND AWARDS
Alma College Trustees’ Scholarship, 1975-79Michigan State Competitive Scholarship, 1975-79Phi Sigma Pi Honor Society, 1979 (converted to Alma College Phi Beta Kappa chapter in 1980)ACS Outstanding Undergraduate Chemistry Student Award, Alma College 1979B.S. degree awarded summa cum laude 1979Pharmacia & Upjohn Special Recognition Awards 1998, 2000Charter Member of the Pharmacia Fellows, 2001Pfizer Achievement Award, 2007UM Collegiate Research Professor Award, 2014
TEACHING EXPERIENCE
Graduate Students Mentored (degree, date, initial postgraduate position(s) attained) Chris George (MS, Sep 2009, “CNS-Permeable Inhibitors of Glucosylceramide
Synthase”, chemist at Ascend Performance Materials) Jessica Bell (PhD, Aug 2012, “Novel Modulators of Rho Transcriptional Signaling in
Cancer”, Assistant Professor of Chemistry at Northern Michigan Univ) Bryan Yestrepsky (PhD, Aug 2013, “Development of a Novel Class of Multifunctional
Virulence-Attenuating Antibiotics”, PSTP Trainee, ACS postdoctoral fellow with Paul Hergenrother at U of Illinois, scientist at AbbVie, Worchester, MA)
Kyle Bolduc (PhD, Aug 2013, “Synthetic and Biocatalytic Methods for the Chemoenzymatic Production of Cryptophycin Analogs”, postdoc at Wolfe Labs, scientist at BASF)
Janice Sindac (PhD, Aug 2014, “Development of Small Molecule Replication Inhibitors Against Western Equine Encephalitis Virus”, scientist at Tetra Discovery Partners, Kalamazoo, MI)
Scott Barraza (PhD, Aug 2014, “Development of Novel Small Molecule Inhibitors of Neurotropic Alphavirus Replication”, postdoc with Scott Denmark at U of Illinois)
Helen Waldschmidt (PhD expected Aug 2017, AHA Predoctoral Fellow 2015-2017) Jeff Zwicker (PhD expected Aug 2018, PSTP Trainee) Brandt Huddle (PhD expected Aug 2018) Dylan Kahl (PhD expected Aug 2019)
Classes MedChem 532 “Bioorganic Principles of Medicinal Chemistry” (University of Michigan,
2007-2015, annual)o Coordinator of course 2012-2015o 6 lectures (introduction and drug metabolism)
MedChem 533 “Strategies in Drug Development” (University of Michigan, 2015)o Creator and coordinator of courseo 6 lectures (lead selection, chirality, conformational restriction, drug metabolism,
drug development case history)
o Proctored and graded eight drug development case history team presentations MedChem 535 “Principles of Drug Design” (University of Michigan, planned to start
Winter 2017, biannual)o Creator and coordinator of courseo New addition to core med chem curriculum
MedChem 635 “Principles of Drug Design” (University of Michigan, 2008, 2011)o Creator and coordinator of courseo 7 lectures (drug metabolism, lead selection, chirality, conformational restriction,
drug development case histories) ChE/Pharm 519 “Modern Pharmaceutical Engineering” (University of Michigan, 2009-
2015)o 1 lecture (medicinal chemistry in drug development)
R21/R33 AI127492-01 (Larsen, Carruthers MPI) 9/1/16-8/31/21“Rational design of CNS-permeable cathepsin L inhibitors for treatment of chronic toxoplasmosis”
R01 GM115459-01A1 (Neubig, PI) 4/1/16-3/31/19“Mechanisms of inhibitors of MRTF/SRF-regulated gene transcription”
R01 AI116605-01A1 (Abramovitch, PI) 12/1/15-11/30/20“Mechanisms of Mycobacterium Tuberculosis pH-driven Adaptation”
R01 HL071818-11A1 (Tesmer, PI) 7/1/15-6/30/19“Structure, function, and inhibition of G protein-coupled receptor kinases”
UH2/UH3 NS092981-01 (Larsen, Shayman MPI) 7/1/15-6/30/20“The Development of Small Molecule Inhibitors for Gaucher Disease Type 3”
R21 AI111182-01 (Trievel, PI) 9/1/14-8/31/16“Homocitrate Synthase Inhibitors as Novel Antifungal Agents for Aspergillus”
R01 AR066049-01 (Larsen, PI) 5/1/14-4/30/17“Inhibition of the Rho/MRTF/SRF pathway as a new treatment for systemic sclerosis”
R01 HD076004 (Larsen, Shayman MPI) 4/1/13-3/31/16“Novel Probes for Studying Treatment of CNS-based Lysosomal Storage Diseases”
P50 GM103297 (Telenitsky, PI) 9/17/12-8/31/17
“The Center for HIV RNA Studies (CRNA)”
P30 CA046592 (Wicha, PI) 9/1/12-8/31/17“University of Michigan Cancer Center Support Grant”
2 R01 GM078200-08 (Rosania, PI) 9/1/12-7/31/16“Chemical Address Tags: A Cheminformatic & Image Data Management and Analysis Plan - admin supplement”
R21 AI096985-01-A1 (Al-Hashimi, PI) 8/1/12-7/31/14“Biological Activity of Lead Compounds Targeting HIV-1 TAR RNA”.
R21 NS079633-01 (Shayman, PI) 8/1/12-7/31/14“In vivo proof of efficacy studies for a novel glucosylceramide synthase inhibitor with central nervous system activity”
R01 AI089417 (Miller, PI) 7/1/10-6/30/15“Novel Therapeutics for Neurotropic Alphaviruses”
R01 GM078200-S1 (Rosania, PI) 7/1/10-8/31/12“Chemical Address Tags: A Cheminformatic & Image Data Management and Analysis Plant”
R01 HL0270973 (Martens, PI) 4/1/10-3/31/14“Trafficking and Regulation of Cardiovascular K+ Channels”
R21 NS065492 01A1 (Larsen, PI) 9/30/09-11/30/11“Design of CNS-Permeable Agents for the Treatment of Lipid Storage Diseases”
R43 DK083074-01A1 (Hilfinger, PI) 4/1/09-3/31/10“Development of orally delivered, non-absorbable AT1 receptor antagonists for inflammatory bowel disease treatment”
P01 HL057346 11A1 (Ginsburg, PI) 4/1/09-3/31/15“Molecular Genetics of Coagulation Disorders”
KEY SCIENTIFIC ACCOMPLISHMENTS
Pharmacia/Pfizer Design and development of hepatoselective inhibitors of hydroxymethylglutaryl-
Coenzyme A (HMG-CoA) reductase. Identification of three clinical candidates. Synthesis and development of novel aminoguanidine antidiabetic/antiobesity agents.
Identification of one clinical candidate. Development of a novel class of inhibitors of AcylCoA:Cholesterol O-Acyltransferase
(ACAT) with in vivo cholesterol-lowering activity. Design and synthesis of novel seco-oxysterol inhibitors of HMG-CoA reductase gene
transcription. Design of peptidomimetic PTP1B inhibitors with submicromolar potency through multiple
parallel synthesis, enzyme-ligand co-crystallization, and structure-based design. Design and synthesis of potent, orally bioavailable non-nucleoside DNA polymerase
inhibitors
University of Michigan Vahlteich Medicinal Chemistry Core (VMCC)
Design of the first glucosylceramide synthase inhibitor that successfully lowers brain glycosphingolipid levels in a mouse model of Sandhoff disease
From a high throughput screening lead, developed inhibitors of neurotropic arboviral RNA replication with protective effects in mouse models of infection. This is the first example of a small molecule therapeutic that lengthens lifespan in a WEEV infection model.
Development of inhibitors of Rho-mediated gene transcription that inhibit cancer cell migration and attenuate up-regulation of pro-fibrotic genes in cells from human scleroderma patients
o CCG-203971 significantly attenuates development of fibrosis in a murine modelo Design of a tag-free photoprobe for target identification that retained biological
activity and was able to specifically label a protein in whole cells Since 2008 the VMCC has collectively contributed to successful grant awards totaling
$41.4 M to the University of Michigan or other external partners (including $8.1 M to the VMCC) in direct costs.
PHARMA PROJECT LEADERSHIP EXPERIENCE
Cholesterol Absorption Inhibitors (2006-2007, Pfizer): Transitioned exploratory project to full Lead Development stage (9 chemists). Contributed to the design of biomarker and early clinical development plans. Managed external contract chemistry support
HMG-CoA Reductase Inhibitors (2003-2006, Pfizer): Led chemistry team of 10-23 chemists in design and synthesis of over 1800 compounds. Advanced three compounds through FIH. Assisted in preparation of INDs and design of early clinical development plans.
Protein Tyrosine Phosphatase 1B (1997-1998, Pharmacia): Leader of international multidisciplinary team (15-20 scientists) working on the design
and development of peptidomimetic inhibitors. Successfully identified compounds with cellular activity.
Antihyperglycemic Compounds (1994-1998, Pharmacia): Chemistry team leader for two different projects developing novel antihyperglycemics. Advanced one compound into FIH (PNU-106817).
CONSULTING
Metabolic Solutions Development Company, Kalamazoo, MI (2008-present)
PROFESSIONAL MEMBERSHIPS
American Chemical Society: Divisions of Organic and Medicinal Chemistry (1985 – present)
PROFESSIONAL SERVICE
ACS Medicinal Chemistry Division Long Range Planning Committee (2005 – 2007)
NIH Special Emphasis Panel for NIH/NIDA RFA “Pharmacological Development of Treatment Agents and Formulations for Tobacco Dependence” (STTR R41), March 18, 2011.
NIH NCATS TRND Contract Reviewer (ZTR1 DPI-3), February 28-March 1, 2013 NIH NINDS NSD-A Study Section, February 22-23, 2016
PUBLICATIONS
Internal:
Eighty-eight full Technical Reports at Upjohn/Pharmacia (1985-2003)
External:
1. Vedejs, E., Larsen, S.D. "Total Synthesis of d,l-Fulvine and d,l-Crispatine," J. Am. Chem. Soc. 1984, 106, 3030-2.
2. Vedejs, E., Larsen, S., West, F.G "Nonstabilized Imidate Ylides by the Desilylation Method: A Route to the Pyrrolizidine Alkaloids Retronecine and Indicine," J. Org. Chem. 1985, 50, 2170-4.
3. Vedejs, E., Larsen, S. "Hydroxylation of Enolates with oxodiperoxymolybdenum-(pyridine)(hexamethylphosphoric triamide): 1,7,7-Trimethyl-3-hydroxybicyclo[2.2.1]-heptan-2-one," Org. Synth. 1985, 64, 127.
4. Larsen, S.D., Grieco, P.A. "Aza Diels-Alder Reactions in Aqueous Solution: Cyclocondensation of Dienes with Simple Iminium Salts Generated under Mannich Conditions," J. Am. Chem. Soc. 1985, 107, 1768-9.
5. Grieco, P.A., Larsen, S.D., Fobare, W.F. "Aza Diels-Alder Reactions in Water: Cyclocondensation of C-Acyl Iminium Ions with Cyclopentadiene," Tetrahedron Lett. 1986, 27, 1975-8.
6. Larsen, S.D., Grieco, P.A., Fobare, W.F. "Reactions of Allylsilanes with Simple Iminium Salts in Water: A Facile Route to Piperidines via an Aminomethano Desilylation-Cyclization Process," J. Am. Chem. Soc. 1986, 108, 3512-13.
7. Grieco, P.A., Larsen, S.D. "An Intramolecular Immonium Ion Variation of the Diels-Alder Reaction: Synthesis of (±)-Dihydrocannivonine," J. Org. Chem. 1986, 51, 3553-5.
8. Vedejs, E., Ahmad, S., Larsen, S.D., Westwood, S. "Synthesis of Monocrotaline by Nucleophilic Macrolactonization," J. Org. Chem. 1987, 52, 3937-8.
9. Larsen, S. D. "A Stereoselective Synthesis of Functionalized Cyclopentenes via Base-Induced Ring Contraction of Thiocarbonyl Diels-Alder Adducts," J. Am. Chem. Soc. 1988, 110, 5932-4.
10. Larsen, S. D., Martinborough, E. "Cycloaddition of ß-Substituted Enones to a Bicyclic Sydnone: Observation of an Unexpectedly Facile Hydrocarbon Elimination," Tetrahedron Lett. 1989, 30, 4625-8.
11.Grieco, P. A., Larsen, S. D. "Immonium Ion Based Diels-Alder Reactions: N- Benzyl-2-azanorbornene," Org. Synth. 1990, 68, 206-9.
12. Larsen, S. D., Spilman, C. H., Bell, F. P., Dinh, D. M., Martinborough, E., Wilson, G. J. Synthesis and Hypocholesterolemic Activity of 6,7-Dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-diones, Novel Inhibitors of AcylCoA:Cholesterol O-Acyltransferase," J. Med. Chem. 1991, 34, 1721-7.
13. Larsen, S.D., Spilman, C.H. "New Potential Therapies for the Treatment of Atherosclerosis," Ann. Rpts. Med. Chem. 1993, 28, 217-26.
14. Larsen, S.D.; Spilman, C.H.; Yagi, Y.; Dinh, D.M.; Hart, K.L.; Hess, G.F. "Design and Synthesis of Seco-Oxysterols Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription", J. Med. Chem 1994, 37, 2343-51.
15. Larsen, S.D. "Regulators of 3-Hydroxy-3-methylglutaryl Coenzyme A Synthesis and Degradation", Drugs of the Future 1995, 20, 919-27.
16. Larsen, S.D.; Fisher, P.V.; Libby, B.E.; Jensen, R.M.; Mizsak, S.A., Watt, W.; Ronk, W.R.; Hill, S.T. "Cyclopentene Synthesis from 1,3-Dienes via Base-Induced Ring Contraction of 3,6-Dihydro-2H-thiopyrans: Studies on Diastereoselection and Mechanism", J. Org. Chem. 1996, 61, 4725-38.
17. Yagi, Y.; Bevis, D.J.; Hart, K.L.; Hess, G.F.; Dinh, D.M.; Keiser, B.J.; Larsen, S.D.; Spilman, C.H. "Screening for Inhibitors of HMG-CoA Reductase Promoter in HepG2: Identification of Four Non-Oxysterol Inhibitors", Drug Dev. Res. 1997, 40, 41-47.
18. May, P.D.; Larsen, S.D. "Preparation of Novel 6-substituted-4-hydroxy-2-pyrone-3-carboxamides and esters via Palladium Catalyzed Cross Coupling Methodology", Synlett 1997, 895-6.
23. Larsen, S.D.; DiPaolo, B.A. “Traceless Solid-Phase Synthesis of 1,2,4-Triazoles Using a Novel Amine Resin”, Org. Lett. 2001, 3, 3341-44.
24. Larsen, S.D.; Barf, T.J.; Liljebris, C.; May, P.D.; Ogg, D.; O'Sullivan, T.J.; Palazuk, B.J.; Schostarez, H.J.; Stevens, F.C.; Bleasdale, J.E. "Synthesis and Biological Activity of a Novel Class of Small Molecular Weight Peptidomimetic Competitive Inhibitors of Protein Tyrosine Phosphatase 1B (PTP1B)", J. Med. Chem. 2002, 45, 598-622.
25. Liljebris, C.; Larsen, S.D.; Ogg, D.; Palazuk, B.J.; Bleasdale, J.E. “Investigation of Potential Bioisosteric Replacements for the Carboxyl Groups of Peptidomimetic Inhibitors of Protein Tyrosine Phosphatase 1B: Identification of a Tetrazole-Containing Inhibitor with Cellular Activity”, J. Med. Chem. 2002, 45, 1785-98.
26. Larsen, S.D.; Stevens, F.C.; Lindberg, T.J.; Bodnar, P.M.; O’Sullivan, T.J.; Schostarez, H.J.; Palazuk, B.J.; Bleasdale, J.E. “Modification of the N-Terminus of Peptidomimetic Protein Tyrosine Phosphatase (PTP1B) Inhibitors: Identification of Analogs with Cellular Activity”, Bioorg. Med. Chem. Lett. 2003, 13, 971-75.
27. Larsen, S.D.; Stachew, C.F.; Clare, P.M.; Cubbage, J.W.; Leach, K.L. “A Catch-and-Release Strategy for the Combinatorial Synthesis of 4-Acylamino-1,3-thiazoles as Potential cdk5 Inhibitors”, Bioorg. Med. Chem. Lett. 2003, 13, 3491-5.
28. Larsen, S.D.; Hester, M.R.; Ruble, J. C.; Kamilar, G.M.; Romero, D.L.; Melchior, E.P.; Sweeney, M.T.; Marotti, K.R. “Discovery and Initial Development of a Novel Class of Antibacterials: Inhibitors of S. aureus Transcription/Translation”, Bioorg. Med. Chem. Lett 2006, 16, 6173-77.
29. Larsen, S.D.; Zhang, Z.; DiPaolo, B.A..; Hageman, T.A.; Hopkins, M.L.; Oien, N.L.; Rohrer, D.C.; Rush, B.D.; Schwende, F.J.; Stefanski, K.J.; Wieber, J.L.; Wilkinson, K.F.; Zamora, K.M. ; Wathen, J.L.; Brideau, R.J “7-Oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamides: Synthesis and Biological Activity of a New Class of Highly Potent Inhibitors of Human Cytomegalovirus DNA Polymerase”, Bioorg. Med. Chem. Lett. 2007, 17, 3840-44.
35. Pfefferkorn, J.A.; Larsen, S.D.; Van Huis, C.; Sorenson, R.; Barton, T.; Winters, T.; Auerbach, B.; Wu, C.; Wolfram, T.J.; Cai, H.; Welch, K.; Esmaiel, N.; Davis, J.; Bousley, R.; Olsen, K.; Bak Mueller, S.; Mertz, T. “Substituted Oxazolidinones as Novel NPC1L1 Ligands for The Inhibition of Cholesterol Absorption”, Bioorg. Med. Chem. Lett. 2008, 18, 546-53.
36. Pfefferkorn, J.A.; Choi, C.; Larsen, S.D.; Auerbach, B.; Hutchings, R.; Park, W.; Askew, V.; Dillon, L.; Hanselman, J.C.; Lin, Z.; Lu, G.H.; Robertson, A.; Sekerke, C.; Harris, M.S.; Pavlovsky, A.; Bainbridge, G.; Caspers, N.; Kowala, M.; Tait, B.D. “Substituted Pyrazoles as Hepatoselective HMG-CoA Reductase Inhibitors: Discovery of PF-3052334 as a Candidate for the Treatment of Hypercholesterolemia”, J. Med. Chem. 2008, 51, 31-45.
37. Park, W.K.C.; Kennedy, R.M.; Larsen, S.D.; Miller, S.; Roth, B.D.; Song, Y.; Steinbaugh, B.A.; Sun, K.; Tait, B.D; Kowala, M.C.; Trivedi, B.K.; Auerbach, B.; Askew, V.; Dillon, L.; Hanselman, J.C.; Lin, Z; Lu, G.H.; Robertson, A.; Sekerke, C. “Hepatoselectivity of Statins: Design and Synthesis of 4-Sulfamoyl Pyrroles as HMG-CoA Reductase Inhibitors”, Bioorg. Med. Chem. Lett. 2008, 18, 1151-56.
38. Sarver, R.W.; Bills, E.; Bolton, G.; Bratton, L.D.; Caspers, N.L.; Dunbar, J.B.; Harris, M.S.; Hutchings, R.H.; Kennedy, R.M.; Larsen, S.D.; Pavlovsky, A.; Pfefferkorn, J.A.; Bainbridge, G. “Thermodynamic and Structure Guided Design of Statin-Based Inhibitors of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase” J. Med. Chem. 2008, 51, 3804-13.
39. Bowles, D.M.; Bolton, G.L.; Boyles, D.C.; Curran, T.T.; Hutchings, R.H.; Larsen, S.D.; Miller, J.M.; Park, W.K.C.; Ritsema, K.G.; Schineman, D.C.; Tamm, M. “Preparation of a HMG-CoA Reductase Inhibitor via an Optimized Imidazole-Forming Condensation Reaction”, Org. Proc. Res. Dev., 2008, 12, 1183-87.
40. Peng, W.; Peltier, D.C.; Larsen, M.J.; Kirchhoff, P.D.; Larsen, S.D.; Neubig, R.R.; Miller, D.J. “The Identification of Thieno[3,2-b]pyrrole Derivatives as Novel Small Molecule Inhibitors of Neurotropic Alphaviruses”, J. Infect. Diseases 2009, 199, 950-57.
41. Evelyn, C.R.; Bell, J.L., Ryu, J.G.; Wade, S.M., Kocab A., Harzdorf, N.L., Showalter, H.D.H., Neubig, R.R., Larsen, S.D. “Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423”, Bioorg. Med. Chem. Lett 2010, 20, 665-72.
42. Okawada, M.; Koga, H.; Larsen, S.D.; Showalter, H.D.; Turbiak, A.J..; Lucas, P.; Xiaohong, J.; Lipka, E.; Hilfinger, J.; Kim, J.S.; Teitelbaum, D.H. “Use of Enterally-Delivered Angiotensin II Type IA Receptor Antagonists to Reduce the Severity of Colitis”, Dig. Dis. Sci. 2011, 56, 2553-65.
43. Yep, A.; Sorenson, R.J.; Wilson, M.W.; Showalter, H.D.H.; Larsen, S.D.; Keller, P.R.; Woodard, R.W. “Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase
(KdsD) from Francisella tularensis”, Bioorg. Med. Chem. Lett. 2011, 21, 2679-82.
44. Pfefferkorn, J.A.; Litchfield, J.; Hutchings, R.; Cheng, X.-M.; Larsen, S.D.; Auerbach, B.A.; Bush, M.R.; Lee, C.; Erasga, N.; Bowles, D.; Boyles, D.C.; Lu, G.; Sekerke, C.; Askew, V.; Hanselman, J.; Dillon, L.; Lin, Z.; Robertson, A.; Olsen, K.; Boustany, C.; Atkinson, K.; Goosen, T.; Sahasrabudhe, V.; Chupka, J.; Duignan, D.B.; Feng, B.; Scialis, R.; Kimoto, E.; Bi, Y.-A.; Lai, Y.; El-Kattan, A.; Bakker-Arkema, R.; Barclay, P.; Kindt, E.; Le, V.; Mandema, J.W.; Milad, M.; Tait, B.D.; Kennedy, R.; Trivedi, B.K.; Kowala, M. “Discovery of Novel Hepatoselective HMG-CoA Reductase Inhibitors for Treating Hypercholesterolemia: A Bench-to-Bedside Case Study on Tissue Selective Drug Distribution”, Bioorg. Med. Chem. Lett. 2011, 21, 2725-31.
45. Fribley, A.; Cruz, P.; Miller, J.; Callaghan, M.; Cai, P.; Narula, N.; Neubig, R.; Showalter, H.; Larsen, S.; Kirchhoff, P.; Larsen, M.; Burr, D.; Schultz, P.; Jacob, R.; Tamayo-Castillo, G.; Sherman, D.; Ron, D.; Kaufman, R. “Complementary Cell-based High Throughput Screens Identify Novel Modulators of the Unfolded Protein Response”, J. Biomol. Screening 2011, 16, 825-35.
46. Puliyappadamba, T; Wu, W.; Polin, L.; Kilkuskie, R.; FinleyR.; Larsen, S.D.; Levi, E.; Miller, F.R.; Wali, A.; Rishi, A.K. “Antagonists of Anaphase Promoting Complex (APC)-2-Cell cycle and Apoptosis Regulatory Protein (CARP)-1 interaction are novel regulators of cell growth and apoptosis”, J. Biol. Chem. 2011, 286, 38000-17.
47. Larsen, S.D.; Wilson, M.W.; Abe, A.; Shu, L.; George, C.H.; Kirchhoff, P.; Showalter, H.W.; Xiang, J.; Keep, R.F.; Shayman, J.A. “Property-based design of a substrate-based gluocosylceramide synthase inhibitor that reduces glucosylceramide levels in the central nervous system”, J. Lipid Res. 2012, 53, 282-91.This article was selected for publication in Global Medical Discovery.
48. Sun, H.; Xu, Y.; Sitkiewicz, I.; Ma, Y.; Wang, X.; Yestrepsky, B.D.; Huang, Y.; Lapadatscu, M.C.; Larsen, M.J.; Larsen, S.D.; Musser, J.M.; Ginsburg, D. “Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice”, Proc. Nat. Acad. Sci. 2012, 109, 3469-74.
49. Sindac, J.S.; Yestrepsky, B.D.; Barraza, S.J.; Bolduc, K.L.; Blakely, P.K.; Keep, R.F.; Irani, D.N.; Miller, D.J.; Larsen, S.D. “Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis”, J Med Chem 2012, 55, 3535-45.
51. Bolduc, K.L.; Larsen, S.D.; Sherman, D.H. “Efficient, Divergent Synthesis of Cryptophycin Unit A Analogues”, JCS Chem. Comm. 2012, 48, 6414-16.
52. Jacob, R.T.; Larsen, M.J.; Larsen, S.D.; Kirchhoff, P.D.; Sherman, D.H.; Neubig, R.R. “MScreen: An Integrated Compound Management and High Throughput Screening (HTS) Data Storage and Analysis System”, J. Biomol. Screening 2012, 17, 1080-87.
53. Ma, Y.; Xu, Y.; Yestrepsky, B.D.; Sorenson, R.J.; Chen, M.; Larsen, S.D.; Sun, H. “Novel inhibitors of Staphylococcus aureus virulence gene expression and biofilm formation”, PLoS ONE 2012, 7, e47225.
54. Yestrepsky, B.D.; Xu, Y.; Sorenson, R.J.; Wilson, M.W.; Ryu, J.; Rajaswaran, W.; Breen, M.E.; Tsume, Y.; Zhang, W.; Li, X.; Sun, D.; Sun, H.; Larsen, S.D. “Novel Inhibitors of Bacterial Virulence: Development of 5,6-Dihydrobenzo[h]quinazoline-4(3H)-ones for the Inhibition of Group A Streptococcal Streptokinase Expression”, Bioorg. Med. Chem. 2013, 21, 1880-97.
55. Arthur, J.R.; Wilson, M.W.; Larsen, S.D.; Shayman, J.A.; Seyfried, T.N. “Ethylenedioxy-PIP2 oxalate reduces ganglioside storage in brain and liver of mice with Sandhoff disease”, Neurochem. Res. 2013, 38, 866-75.
56. Bell, J.L.; Haak, A.J.; Wade, S.M.; Sun, Y.; Neubig, R.R.; Larsen, S.D. “Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway”, Beilstein J. Org. Chem. 2013, 9, 966-73.
57. Bell, J.L.; Haak, A.J.; Wade, S.M., Kirchhoff, P.D.; Neubig, R.R.; Larsen, S.D. “Optimization of Novel Nipecotic Bis(amide) Inhibitors of the Rho/MKL1/SRF Transcriptional Pathway as Potential Anti-metastasis Agents”, Bioorg. Med. Chem. Lett. 2013, 23, 3826-32.
61. Homan, K.T.; Wu, E.; Wilson, M.W.; Singh, P.; Larsen, S.D.; Tesmer, J.J.G. “Structural and Functional Analysis of G Protein-Coupled Receptor Kinase Inhibition by Paroxetine and a Rationally Designed Analog”, Mol. Pharmacol. 2014, 85, 237-48.
62. Yestrepsky, B.D.; Kretz, C.; Xu, Y.; Holmes, A.; Sun, H.; Ginsburg, D.; Larsen, S.D. “Development of tag-free photoprobes for studies aimed at identifying the target of novel Group A Streptococcus antivirulence agents”, Bioorg. Med. Chem. Lett. 2014, 24, 1538-44.
63. Larsen, M.J.; Larsen, S.D.; Fribley, A.; Grembecka, J.; Haak, A; Homan, K.; Mapp, A.; Nikolovska-Coleska, Z.; Stuckey, J.A.; Sun, D.; Sherman, D.H. “The Role of HTS in Drug Discovery at University of Michigan”, Combi. Chem. & High Throughput Screening 2014, 17, 210-30.
64. Baez-Santos, Y.M.; Barraza, S.J.; Wilson, M.W.; Agius, M.P.; Mielech, A.; Davis, N.M.; Baker, S.C.; Larsen, S.D.; Mesecar, A.D. “X-Ray Structural and Biological Evaluation of a
Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain Like-Proteases”, J. Med. Chem., 2014, 57, 2393-2412.
65. Haak, A.; Tsou, P.-S.; Amin, M.A.; Ruth, J.H.; Campbell, P.; Fox, D.A.; Khanna, D.; Larsen, S.D.; Neubig, R.R. “Targeting the myofibroblast genetic switch: inhibitors of MRTF/SRF-regulated gene transcription prevent fibrosis in a murine model of skin injury”, J. Pharmacol. Exp. Ther. 2014, 349, 480-86.
66. Shayman, J.A.; Larsen, S.D. “The Development and Use of Small Molecule Inhibitors of Glycosphingolipid Metabolism for the Treatment of Lysosomal Storage Disease”, J. Lipid Res. 2014, 55, 1215-25.
67. Delekta, P.C.; Dobry, C.J.; Sindac, J.A.; Barraza, S.J.; Blakely, P.K.; Xiang, J.; Kirchhoff, P.D.; Keep, R.F.; Irani, D.N.; Larsen, S.D.; Miller, D.J. “Novel indole-2-carboxamide compounds are potent broad spectrum antivirals active against western equine encephalitis virus in vivo”, J. Virology 2014, 88, 11199-11214.
68. Deng, X.; Agnihothram, S.; Mielech, A.M.; Nichols, D.B.; St. John, S.; Wilson, M.W.; Larsen, S.D.; Mesecar, A.D.; Lenschow, D.J.; Baric, R.; Baker, S.C. “A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-like Proteases of Emerging Coronaviruses”, J. Virology 2014, 88, 11825-33.
69. Barraza, S.J.; Delekta, P.C.; Sindac, J.A.; Dobry, C.J.; Xiang, J.; Keep, R.F.; Miller, D.J.; Larsen,S.D. “Discovery of Anthranilamides as a Novel Class of Inhibitors of Neurotropic Alphavirus Replication”, Bioorg. Med. Chem 2015, 23, 1569-87.
71. Min, K.A.; Rajeswaran, W.G.; Oldenbourg, R.; Harris, G.; Keswani, R.K.; Chiang, M.; Rzeczycki, P., Talattof, A.; Hafeez, M.; Horobin, R.W.; Larsen, S.D.; Stringer, K.A.; Rosania, G.R. “Massive Bioaccumulation and Self-Assembly of Phenazine Compounds in Live Cells”, Adv. Sci. 2015 2, 1500025.
72. Homan, K.T.; Waldschmidt, H; Glukhova, A.; Cannavo, A.; Song, J.; Cheung, J.Y.; Koch, W.J.; Larsen, S.D.; Tesmer, J.J.G. “Crystal Structure of G Protein-Coupled Receptor Kinase 5 in Complex with a Rationally Designed Inhibitor “, J. Biol. Chem. 2015 290, 20649-59. This article was selected as a JBC Paper of the Week.
73. Muthu, M.; Somagoni, J.; Cheriyan, V.T.; Munie, S.; Levi, E.; Ashour, A.E.; Alaa, E.B.; Alafeefy, A.M.; Sochacki, P.; Polin, L.A.; Reddy, K.B.; Larsen, S.D.; Singh, M.; Rishi, A.K. “Identification and testing of novel CARP-1 functional mimetic compounds as inhibitors of non-small cell lung and triple negative breast cancers”, J. Biomed. Nanotech. 2015 11, 1608-27.
74. Waldschmidt, H.; Homan, K.; Cruz-Rodriguez, O.; Cato, M.; Waninger-Saroni, J.; Larimore, K.; Cannavo, A.; Song, J.; Cheung, J.; Koch, W.; Tesmer, J.; Larsen, S.D. “Structure-Based Design, Synthesis and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors”, J. Med. Chem. 2016 59, 3793-
3807.
75. Bolinger, M.; Ramshekar, A.; Waldschmidt, H.; Larsen, S.; Bewley, M.; Flanagan, J.; Antonetti, D. “Occludin S471 phosphorylation contributes to epithelial monolayer maturation”, Mol. Cell Biol. 2016 36, 2051-66.
76. Airik, M.; Krook, M.A.; Pedersen, E.A.; Larsen, S.D.; Neubig, R.R.; Lawlor, E.R. “Rho-GTPase-dependent cell state transitions mediate phenotypic plasticity in aggressive pediatric solid tumors via a Rac1-MKL signaling axis”, Mol. Cell. Biol. submitted for publication.
77. Beck, M.W.; Kerr, R.A.; Derrick, J.S.; Oh, S.B.; Cho, W.J.; Lee, S.J.C.; Tehrani, Z.A.; Suh, N.; Kim, S.; Ji, Y.; Larsen, S.D.; Kim, K.S.; Lee, J.-Y.; Ruotolo, B.T.; Lim, M.H. “Engineering structure-mechanism-based chemical regulators for distinct pathological factors in Alzheimer’s disease”, Nat. Chem. submitted for publication.
78. Yu-Wai-Man, C.; Hutchings, K.; Lisabeth, E.M.; Spender-Dene, B.; Lee, R.M.H.; Bailly, M.; Treisman, R.; Larsen, S.D.; Neubig, R.R.; Khaw, P.T. “Local delivery of a novel MRTF/SRF inhibitor, CCG-222740, prevents scar tissue formation in a preclinical model of conjunctival fibrosis”, Science Trans. Med., submitted for publication.
79. Zheng, H.; Colvin, C.J.; Johnson, B.K.; Kirchhoff, P.; Wilson, M.; Jorgensen-Muga, K.; Larsen, S.D.; Abramovitch, R.B. “Inhibition of Mycobacterium tuberculosis persistence using chemical inhibitors of the DosRST two-component regulatory system”, Nat. Chem. Biol. submitted for publication.
80. Haak, A.J.; Appleton, K.M.; Mathes, E.; Misek, S.; Ji, Y.; Wade, S.M.; Bell, J.L.; Rockwell, C.E.; Airik, M.; Krook, M.A.; Larsen, S.D.; Verhaegan, M.; Lawlor, E.R.; Neubig, R.R. “Pharmacological inhibition of Myocardin-related transcription factor pathway blocks lung metastasss of RhoC overexpressing melanoma”, Mol. Canc. Ther. submitted for publication.
81. Cheriyan, V.T; Muthu, M.; Sekhar, S.; Patel, K.; Larsen, S.D.; Polin, L.; Levi, E.; Singh, M.; Rishi, A.K. “CARP-1 Functional Mimetics are novel inhibitors of drug-resistant triple negative breast cancers”, Oncotarget submitted for publication.
PRESENTATIONS
1. Larsen, S. D., "A Stereoselective Synthesis of Functionalized Cyclopentenes via Base-Induced Ring Contraction of Thiocarbonyl Diels-Alder Adducts", Gordon Conference on Chemistry of Heterocyclic Compounds, New Hampton, NH, July 11-15, 1988.
2. Larsen, S. D., Martinborough, E., "Cycloaddition of Beta-Substituted Enones to a Bicyclic Sydnone: Observation of an Unexpectedly Facile Hydrocarbon Elimination", Gordon Conference on Chemistry of Heterocyclic Compounds, New Hampton, NH, July 10-14, 1989.
3. Larsen, S. D., Spilman, C. H., Bell, F. P., Dinh, D. M., Martinborough, E., Wilson, G. J., "Synthesis and Hypocholesterolemic Activity of 6,7-Dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-diones, Novel Inhibitors of AcylCoA:Cholesterol O-Acyltransferase", 201st National Meeting of the American Chemical Society, Division of Medicinal Chemistry, Atlanta, GA, April 14-19, 1991.
4. Larsen, S.D., Spilman, C.H., Dinh, D.M., Hart, K.L., Hess, G.F., Yagi, Y., "Synthesis of a Seco-Oxysterol Inhibitor of HMG-CoA Reductase Gene Transcription", 206th National American Chemical Society Meeting, Division of Medicinal Chemistry, Chicago, IL, August 22-27, 1993.
5. Larsen, S.D., Spilman, C.H., Dinh, D.M., Hart, K.L., Hess, G.F., Yagi, Y., "Synthesis of a Seco-Oxysterol Inhibitor of HMG-CoA Reductase Gene Transcription", 24th National Medicinal Chemistry Symposium, Salt Lake City, UT, June 21-25, 1994 .
6. Larsen, S.D., Fisher, P.V., Libby, B.E., Mizsak, S.A., Watt, W., "Cyclopentene Synthesis via Base-Catalyzed Ring Contraction of 3,6-Dihydro-2H-thiopyrans: Studies on Diastereoselection and Mechanism", 208th National American Chemical Society Meeting, Division of Organic Chemistry, Washington, D.C., August 21-26, 1994.
7. Watt, W., Fisher, P.V., Larsen, S.D., "A Comparison of Area Detector X-ray Diffraction Data with Conventional Diffractometer Data for Some Functionalized Cyclopentenes", 1995 Montreal American Crystallographic Association Meeting, Montreal, Quebec, Canada, July 23-28, 1995.
8. Stevens, F.C.; Larsen, S.D., Martinborough, E.A., Burr, J.E., Connell, M.A., Shattuck, M.H., “Novel Phenylglycine-based Insulin Sensitizers: An Investigation of the Role of the alpha-Amino Acid Moiety in Antihyperglycemic Activity”, 214th National ACS Meeting, Division of Medicinal Chemistry, Las Vegas, NV, September 7-11, 1997.
9. May, P.D.; Larsen, S.D. “Concise Synthesis of Novel 6-Substituted 2-Pyrones via Palladium-Catalyzed Cross-Coupling Methodology”, 214th National ACS Meeting, Division of Organic Chemistry, Las Vegas, NV, September 7-11, 1997.
10. Cudahy, M.M.; Connell, M.A., Larsen, S.D.; May, P.D.; Meglasson, M.D.; Tanis, S.P.; Tegley, C.M.; Tucker, J.A.; Vaillancourt, V. “Aminoguanidines and Related Compounds as Antidiabetic Agents”, 215th National ACS Meeting, Division of Medicinal Chemistry, Dallas, TX, March 29 - April 2, 1998.
11. Stevens, F.C. ; Larsen, S.D.; Connell, M.A.; Cudahy, M.M.; Evans, B.R.; May, P.D.; Meglasson, M.D.; Tanis, S.P.; Vaillancourt, V.A. “Development of Amino- and Diaminoguanidine Antidiabetic Agents”, 215th National ACS Meeting, Division of Medicinal Chemistry, Dallas, TX, March 29 - April 2, 1998.
12. Larsen, S.D. ; Connell, M.A.; Cudahy, M.M.; Evans, B.R.; May, P.D.; Meglasson, M.D.; Stevens, F.C.; Tegley, C.M.; Tanis, S.P.; Vaillancourt, V.A. “Development of Amino- and Diaminoguanidine Antidiabetic Agents”, French American Chemical Society Meeting (FACS VII), Cannes, France, June 2-6, 1998.
13. Larsen, S.D. ; Bannow, C.A; Barf; Colca, J.R.; Herbert, N.; Laborde, A.L.; Liljebris, C.; Lindberg, T.J.; May, P.D.; Nilsson, M.C.; Ogg, D.; O'Sullivan, T.J.; Palazuk, B.J.; Rutherford-Root, K.L.; Schostarez, H.J.; Smith, C.W.; Stevens, F.C.; Stuchley, C.J.; Bleasdale, J.E. "Synthesis, Biological Activity and Enzyme-Ligand Co-crystallography of Small Molecular Weight Competitive Inhibitors of Protein Tyrosine Phosphatase 1B", invited lecture at Symposium on New Advances in Protein Tyrosine Phosphatase Inhibitors, 219th National ACS Meeting, San Francisco, California, March 26, 2000.
14. Larsen, S.D. ; Bannow, C.A; Barf; Colca, J.R.; Herbert, N.; Laborde, A.L.; Liljebris, C.; Lindberge, T.J.; May, P.D.; Nilsson, M.C.; Ogg, D.; O'Sullivan, T.J.; Palazuk, B.J.; Rutherford-Root, K.L.; Schostarez, H.J.; Smith, C.W.; Stevens, F.C.; Stuchly, C.W.; Bleasdale, J.E. "Synthesis, Biological Activity and Enzyme-Ligand Co-crystallography of Small Molecular Weight Competitive Inhibitors of Protein Tyrosine Phosphatase 1B", invited lecture at Montana State University, Bozeman, Montana, September 22, 2000.
15. Bleasdale, J.E .; Larsen, S.D. "Protein Tyrosine Phosphatases as Drug Targets: PTP1B and Diabetes", invited lecture at Symposium on Signal Transduction, 33rd Central/Great Lakes Midwest Joint Regional ACS Meeting, Grand Rapids, Michigan, June 11-13, 2001.
16. Larsen, S.D. “Drug Discovery from an Academic Perspective: The UM Medicinal Chemistry Core Synthesis Lab”, invited lecture at University of Michigan for INTMED/Pharm602 class: Drug Development and Clinical Trials, January 24, 2008.
17. Fribley, A.M.; Larsen, M.J.; Cai, P.; Nerula, N.; Showalter, H.D.; Neubig, R.R.; Larsen, S.D.; Kaufman, R.J. “Complementary Cell-Based Screens Identify Specific Inhibitors of the Unfolded Protein Response Apoptotic Sub-Pathway and Reduce False Positive Hits”, Society for Biomolecular Sciences 14th Annual Meeting, St. Louis, Missouri, April 6-10, 2008.
18. Evelyn, C.R .; Ryu, J.G.; Larsen, S.D.; Showalter, H.D.; Neubig, R.R. “Structure Activity Relationship Study of CCG-1423, an Inhibitor of Rho/MKL1-stimulated Gene Transcription”, American Association for Cancer Research Annual Meeting, San Diego, California, April 12-16, 2008.
19. Pfefferkorn, J.A .; Choi, C.; Larsen, S.D. et al. “Pyrazoles as Hepatoselective HMG-CoA Reductase Inhibitors: Discovery and Early Clinical Evaluation of PF-3052334 for the Treatment of Hypercholesterolemia”, National Medicinal Chemistry Symposium, Abstract NMCS-124, Pittsburgh, PA, June, 2008.
20. Okawada, M. ; Koga, H.; Larsen, S.D.; Showalter, H.D.; Turbiak, A.J.; Jin, X.; Lucas, P.C.; Teitelbaum, D.H. “Use of Enterally-delivered Angiotensin II Type Ia Receptor Antagonists to Reduce the Severity of Colitis”, Annual Moses Gunn Surgery Conference, University of Michigan, Ann Arbor, MI, 2009.
21. Okawada, M. ; Koga, H.; Larsen, S.D.; Showalter, H.D.; Turbiak, A.J.; Jin, X.; Lucas, P.C.; Teitelbaum, D.H. “Use of Enterally-delivered Angiotensin II Type Ia Receptor Antagonists to Reduce the Severity of Colitis”, Digestive Disease Week of American Gastroenterology Association Annual Conference, Chicago, IL, 2009.
22. Larsen, S.D. “Medicinal Chemistry and Drug Discovery”, invited lecture at University of Michigan for Ch/E Pharm 519 class: Modern Pharmaceutical Engineering, February 10, 2009.
23. Larsen, S.D. “Medicinal Chemistry and Pharmaceutical Industry Research”, invited lecture at University of Michigan for Translational Strategies for ChE/BME/Pharm 596 class: Quality and Efficiency in Pharmaceutical Innovation, September 15, 2009.
24. Larsen, S.D. “From Product Optimization to Target Identification: An Incredible Journey from Industry to Academics”; invited lecture at Paul A. Grieco 65th Birthday Symposium;
Montana State University, Bozeman, MT; September 26, 2009.
25. Larsen, S.D . “Design and Development of Highly Hepatoselective Inhibitors of HMG-CoA Reductase”, Medicinal Chemistry Department Seminar Series, University of Michigan, April 1, 2010.
26. Xu, Y .; Ma, Y.; Larsen, S.D.; Ginsburg, D.; Sun, H. “Small Chemical Compound Inhibits Staphylococcus aureus Virulence and Accelerates HNP-1-Mediated Cell Death”, ATVB 2010, San Francisco, CA, April 8-10, 2010.
27. Larsen, S.D. “Drug Candidate Discovery”; invited lecture at University of Michigan for PIBS 507 class: Introduction to Translational Research, January 18, 2011.
28. Larsen, S.D. “Medicinal Chemistry and Drug Discovery”, invited lecture at University of Michigan for Ch/E Pharm 519 class: Modern Pharmaceutical Engineering, February 8, 2011.
29. Bell, J.L .; Evelyn, C.R.; Ryu, J.G.; Wade, S.M.; Neubig, R.R.; Larsen, S.D. “Searching for the macromolecular target(s) of novel modulators of Rho signaling that inhibit prostate cancer metastasis”, 241st National ACS Meeting, Anaheim, CA, March 27-31, 2011 (MEDI-107).
30. Larsen, S.D. “The University of Michigan Vahlteich Medicinal Chemistry Core: Leading Basic Biomedical Research down the Path of Drug Discovery”, invited lecture at Wayne State University, Detroit, MI, April 6, 2011.
31. Yestrepsky, B. ; Kretz, C.; Xu, Y.; Ginsburg, D.; Sun, H.; Larsen, S. “Virulence-attenuating inhibitors of streptokinase (SK) expression in Group A streptococcus (GAS): Activity optimization and target identification”, 242nd ACS National Meeting, Denver, CO, August 28 – September 1, 2011 (MEDI-91).
32. Kong, W .; Burkart, A.; Chen, M.; Jin, W.; Hirshmann, M.; Goodyear, L.; Neubig, R.; Larsen, S.; Allen, P. Teg Pipes, C.G.; Bassel-Duby, R.; Olson, E.; Patti, M.-E. “Genetic or Pharmacologic Inhibition of the STARS-SRF Pathway Increases AMPK Phosphorylation and Oxidative Metabolism”, 72nd American Diabetes Assoc. Scientific Sessions, Philadelphia, PA, June 8-12, 2012.
33. Larsen, S.D. “Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis”, invited lecture at Loyola University, Chicago, IL, March 22, 2012.
34. Sindac, J.A. ; Barraza, S.; Bolduc, K.; Yestrepsky, B.; Irani, D.; Miller, D.; Larsen, S. “Small molecule antivirals against western equine encephalitis virus”, 243rd ACS National Meeting, San Diego, CA, March 25-29, 2012 (MEDI-170).
35. Barraza, S.J .; Sindac, J.A.; Bolduc, K.; Yestrepsky, B.; Keep, R.F.; Miller, D.J.; Larsen, S.D. “Development of novel small molecule inhibitors of alphavirus replication”, 243rd ACS National Meeting, San Diego, CA, March 25-29, 2012 (MEDI-168).
36. Yestrepsky, B.D. ; Kretz, C.; Xu, Y.; Ma, Y.; Holmes, A.; Sun, H.; Ginsburg, D.; Larsen, S.D. “SAR development and target identification studies on a class of novel bacterial
virulence inhibitors”, 244th ACS National Meeting, Philadelphia, PA, August 19-23, 2012 (MEDI-260).
37. Bolduc, K.L. , Larsen, S.D., Sherman, D.H. “Chemoenzymatic synthesis of novel cryptophycin anticancer agents”, 244th ACS National Meeting, Philadelphia, PA, August 19-23, 2012 (MEDI-57).
38. Larsen, S.D. “Development of Novel Inhibitors of Neurotropic Alphaviruses”, invited lecture at UM CDNM Lecture Series, Palmer Commons, University of Michigan, September 7, 2012.
39. Larsen, S.D. “Novel Inhibitors of Neurotropic Alphavirus RNA Replication”, invited lecture at NERCE Medicinal Chemistry and Preclinical Development Workshop, MIT Broad Institute, Cambridge, MA, September 21, 2012.
40. Larsen, S.D. “Medicinal Chemistry in Drug Discovery”, invited lecture at Symposium on Therapeutics Discovery & Development: Navigating the Critical Path”, Institute for Clinical and Translational Research, University of Wisconsin, Madison, WI, February 10, 2014.
41. Barraza, S.J .; Sindac, J.A.; Dobry, C.J.; Xiang, J.; Blakely, P.K.; Irani, D.N.; Keep, R.F.; Miller, D.J.; Larsen, S.D. “Development of novel small molecule antivirals for Western equine encephalitis virus”, 247th ACS National Meeting, Dallas, TX, March 16-20, 2014 (MEDI-347).
42. Sindac, J.A .; Barraza, Scott J.; Dobry, C.J.; Xiang, J.; Blakely, P.K.; Irani, D.N.; Keep, R.F.; Miller, D.J.; Larsen, S.D.. “Development of small molecule inhibitors against neurotropic alphavirus replication”, 247th ACS National Meeting, Dallas, TX, March 16-20, 2014 (MEDI-345).
43. Haak, A .; Tsou, P.-S.; Fox, D.A.; Khanna, D.; Larsen, S.D.; Neubig, R.R. “Modulating myofibroblast transition in systemic sclerosis through inhibition of Rho/MRTF regulated transcription”, ASPET Annual Meeting at Experimental Biology 2014, San Diego, CA, April 26-30, 2014.
44. Waldschmidt, H. ; Homan, K.; Larimore, K.; Tesmer, J.; Larsen, S. “Development of selective GRK2 inhibitors for the treatment of heart failure”, 248th ACS National Meeting, San Francisco, CA, August 10-14, 2014 (MEDI-47).
45. Larsen, S.D. “From Hit to Probe: Achieving In Vivo Activity with Medicinal Chemistry”, invited lecture at Drug Discovery & Development Bootcamp, University of Michigan, Ann Arbor, MI, March 16, 2015.
46. Larsen, S.D. "The University of Michigan Vahlteich Medicinal Chemistry Core: Achieving Proof-of-Concept in Vivo for Novel Therapeutic Hypotheses”, invited lecture at 2015 Great Lakes/Central Regional ACS Meeting, May 27-29, 2015 (JGLCRM 31).
47. Carruthers, V.B; Zwicker, J.; Haug, N.; Banda, A.; Diaz, N; Schultz, T.L.; DiCristina, M.; Larsen, S.D. “Targeting a T. gondii cathepsin protease essential for chronic toxoplasmosis” Keystone Symposia on Molecular and Cellular Biology, Drug Discovery
for Parasitic Diseases, Tahoe City, CA, January 24-28, 2016.
48. Waldschmidt, H.V .; Homan, K.T.; Cruz-Rodriguez, O.; Cato, M.; Larimore, K.; Cannavo, A.; Song, J.; Cheung, J.Y.; Koch, W.J.; Tesmer, J.J.G.; Larsen, S.D., “Development of Selective GRK2 inhibitors for the Treatment of Heart Failure”, Keystone Symposia on Molecular and Cellular Biology, G Protein-Coupled Receptors: Structure, Signaling and Drug Discovery, February 21-25, 2016.
49. Larsen, S.D. "The University of Michigan Vahlteich Medicinal Chemistry Core: Achieving Proof-of-Concept in Vivo for Academic Drug Discovery”, invited lecture, Michigan State University Department of Pharmacology & Toxicology Seminar Series, March 11, 2016.
50. Diaz, N .; Zwicker, J.; Larsen, S.; Carruthers, V. “Design and synthesis of potential CNS-permeable inhibitors of T. gondii Cathepsin L”, 251st ACS National Meeting, San Diego, CA, March 13-17, 2016 (MEDI-99).
PATENTS AND PUBLISHED APPLICATIONS (PHARMA)
1. US 5,132,424: Pyrazolo-pyrrolo-pyrimdine-diones.
2. US 5,523,318: Pyrrolidino-substituted oximes useful as anti-atherosclerosis and anti-hypercholesterolemic agents.
3. US 5,565,468: Pyridino substituted oximes useful as anti-atherosclerosis and anti-hypercholesterolemic agents.
4. US 5,597,816: Pyrazoloazepino substituted oximes useful as anti-atherosclerosis and anti-hypercholesterolemic agents.
5. US 5,723,476: 4-Hydroxycoumarin-3-carboxamides for the treatment of diabetes mellitus.
6. US 5,955,617: Aminoguanidine carboxylate lactams for the treatment of non-insulin-dependent diabetes mellitus.
7. US 5,994,577: Aminoguanidine carboxylates for the treatment of non-insulin-dependent diabetes mellitus.
8. US 6,166,080: Aminoguanidine carboxylates for the treatment of obesity.
9. US 6,177,453: Aminoguanidine carboxylate lactams for the treatment of non-insulin-dependent diabetes mellitus.
10. US 6,184,216: Aminoguanidine carboxylate lactams for the treatment of non-insulin-dependent diabetes mellitus.
11. US 6,274,580: Aminoguanidine carboxylate lactams for the treatment of non-insulin-dependent diabetes mellitus.
12. US 6,329,545: Aminoguanidine carboxylates for the treatment of non-insulin-dependent diabetes mellitus.
13. US 6,353,023: Inhibitors of protein tyrosine phosphatases.
14. US 6,410,585: Inhibitors of protein tyrosine phosphatases.
15. US 6,458,788: 4-Hydroxycinnoline-3-carboxyamides as antiviral agents
16. US 6,624,160: 4-Oxo-1,4-dihydro-3-cinnolinecarboxamides as antiviral agents
17. US 6,852,731: Antiviral compounds
18. US 6,861,438: Antiviral agents
19. WO200204444: Heterocycle carboxamides as antiviral agents.
20. WO200204443: Heterocycle carboxamides as antiviral agents.
21. WO2003059912: Preparation of 7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamides as antiviral compounds.
22. WO2003059878: Preparation of 7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamides as antiviral compounds.
23. US2004138449: A preparation of thieno[2,3-b]pyridinecarboxamide derivatives, useful as antiviral agents
24. WO2005079790: Preparation of imidazole-based HMG-CoA reductase inhibitors
25. WO2006087630: Preparation of pyrazolyloxy hexanoic acid derivatives as HMG CoA reductase inhibitors
26. WO2008104875: Oxazolidinones as cholesterol absorption inhibitors
27. WO2010105048: Preparation of benzylthiazolidinedione derivatives for use as PPAR modulators
28. WO2011075514: PPAR-sparing thiazolidinediones and combinations for the treatment of neurodegenerative diseases.
29. WO2011084453: PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
30. WO2011084456: PPAR-sparing thiazolidinediones and combinations for the treatment of diabetes mellitus and other metabolic diseases
31. WO2011084459: PPAR-sparing thiazolidinediones and combinations for the treatment of obesity and other metabolic diseases
32. WO2011133442: Novel synthesis for thiazolidinedione compounds
33. WO2012021467: A process for the preparation of thiazolidinedione derivatives for use as PPAR receptor modulators
34. WO2012178142: Prepration of indolylmethylphenoxypropranoic acid derivatives and analogs for use as PPAR modulators.
35. WO 2012177956: Preparation of phenyloxoethylphenylacrylate derivatives and analogs for use as PPAR modulators
36. WO2015013187: Preparation of phenylalkylhydroxamate derivatives for use in the treatment of metabolic diseases
PATENTS AND PUBLISHED APPLICATIONS (UNIVERSITY OF MICHIGAN)
1. US 8,293,776: Compositions and methods for treating inflammatory conditions of the bowel.
2. US 8,501,722: Methods and compositions for treating bacterial infection
3. US 8,846,684: Arbovirus inhibitors and uses thereof.
4. US 8,946,424: Deuterated amlexanox
5. US 8,961,959: Glucosylceramide Synthase Inhibitors and Therapeutic Methods Using the Same
6. US 9,365,581: Deuterated amlexanox
7. WO2011035143: Benzamides and related compounds as RhoGTPase inhibitors and their preparation and compositions for inhibiting Rho-mediated diseases and conditions.
8. US20120252807: Preparation of pyrrolyl(or imidazolyl) piperidinyl methanone derivatives as arbovirus inhibitors
9. WO2012149335: Preparation of thiadiazolidinone derivatives as inhibitors of RGS proteins
10. US 20130095089: Glucosylceramide synthase inhibitors and therapeutic methods using the same.
11. WO 2013033392: Antitumor compounds.
12. WO2013166282: Preparation of benzoquinazoline derivatives for treating bacterial infection.
13. WO2014085485: Methods and compositions for targeting cancer stem cells.
14. WO 2014179734: Preparation of deuterated amlexanox derivatives for use as TBK1 or IKKε protein kinase inhibitors
15. US20150250769: Methods and compositions for inhibiting Rho/MRTF-mediated diseases and conditions
16. WO2016023028: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
17. WO2016073847: Preparation of substituted piperidine-3-carboxamides as inhibitors of myocardin-related transcription factor and serum response factor (MRTF/SRF)-mediated gene transcription
