Edmund Ellsworth, PhD

Professor (Fixed-Term) and Medicinal Chemistry Facility Director
Pharmacology & Toxicology

Bio

Transforms science into drug candidates and chemical probes. Scientific leader, mentor and program leader with achievements including 11 development candidates. Co-founder of two start-up companies, Management or internal scientists and a of up to >30 internal and external FTEs, enhancing overall productivity 500%, NIH reviewer. Applies technologies, while bringing a sense of urgency, strategic focus, and accountability. A stabilizing influence and a believer of leading by forming partnerships. • Small molecule and peptide therapeutic (antibacterials) drug discovery • Therapeutic area expertise: antibacterials, antivirals, CNS diseases muscle growth, dermal scarring, sexual antagonism, antiparasitics, oncology and inflammation • Target expertise: topoisomerases, kinases, proteases, nuclear hormone receptors, ion channels, ribosome, membrane binding, GPCRs, metalloenzymes, hydrolases, and synthetases • Medicinal chemistry, API process development, and chemoinformatics • Intellectual property development • Early candidate drug development • Structure-based and computer-aided drug design • High throughput screening (HTS), triage including natural product screening • ADME, pharmacokinetics, toxicokinetics • Portfolio management and resourcing • Business development / academic alliances / due diligence including contract negotiations. • Project planning, leadership and budget management • CRO management • NIH, DOD, SBIR/STTR Proposal Development

Colleges

• College of Osteopathic Medicine

Associations

• MSU Drug Discovery

Facilities

• Medicinal Chemistry Facility

Education

• Post-doctoral Fellwo, Chemistry, Harvard University (1990-07-04—1992-09-04)
• Ph.D., Chemistry, University of California, Santa Barbara (1986-08-25—1990-07-01)
• B.S., Chemistry, California State University, Chico (1983-09-07—1986-05-25)

Education

• QQQ 1Post-doctoral Fellwo, 2Chemistry, 3Harvard University 4Chemistry (1990-07-04—1992-09-04)
• QQQ 1Ph.D., 2Chemistry, 3University of California, Santa Barbara 4Chemistry (1986-08-25—1990-07-01)
• QQQ 1B.S., 2Chemistry, 3California State University, Chico 4Chemistry (1983-09-07—1986-05-25)

Works

• Lipid-Based Self-Microemulsion of Niclosamide Achieved Enhanced Oral Delivery and Anti-Tumor Efficacy in Orthotopic Patient-Derived Xenograft of Hepatocellular Carcinoma in Mice. International journal of nanomedicine (2024-03-14)
• The Novel RXR Agonist MSU-42011 Differentially Regulates Gene Expression in Mammary Tumors of MMTV-Neu Mice. International Journal of Molecular Sciences (2023-02-21)
• Anti-fibrillization effects of sulfonamide derivatives on α-synuclein and hyperphosphorylated tau isoform 1N4R. Journal of Molecular Structure (2022)
• Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma. Biomedicines (2022-04-19)
• Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma. Biomedicines (2022-04-19)
• Machine Learning Analysis of Cocaine Addiction Informed by DAT, SERT, and NET-Based Interactome Networks. Journal of Chemical Theory and Computation (2022-04-12)
• Structural basis of binding and inhibition of ornithine decarboxylase by 1-amino-oxy-3-aminopropane. Biochemical Journal (2021-12-10)
• The RXR Agonist MSU42011 Is Effective for the Treatment of Preclinical HER2+ Breast Cancer and Kras-Driven Lung Cancer. Cancers (2021-10-06)
• The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer. Scientific Reports (2020-12-17)
• Therapeutic potential of targeting mixed lineage kinases in cancer and inflammation. Pharmacology & Therapeutics (2020)
• Inhibiting Mycobacterium tuberculosis DosRST Signaling by Targeting Response Regulator DNA Binding and Sensor Kinase Heme. ACS Chemical Biology (2020-01-17)
• Spermine in semen of male sea lamprey acts as a sex pheromone. PLOS Biology (2019-07-09)
• Spermine in semen of male sea lamprey acts as a sex pheromone. PLoS biology (2019-07-09)
• Identification of new MmpL3 inhibitors by untargeted and targeted mutant screens defines MmpL3 domains with differential resistance. (2019-02-28)
• Inhibition of Mycobacterium tuberculosis DosRST two-component regulatory system signaling by targeting response regulator DNA binding and sensor kinase heme. (2018-09-08)
• Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis. Molecules (2018-06-06)
• The discovery of isoxazoline oxime ethers as a new class of ectoparasiticides for the control of Haematobia irritans (horn fly) in cattle. Bioorganic & Medicinal Chemistry Letters (2014)
• Stereoselective Synthesis of (S)-3-(Methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile. The Journal of Organic Chemistry (2012-05-18)
• Discovery of a series of 2-(1H-pyrazol-1-yl)pyridines as ALK5 inhibitors with potential utility in the prevention of dermal scarring. Bioorganic & Medicinal Chemistry Letters (2012)
• Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorganic & Medicinal Chemistry Letters (2008)
• Synthesis and antibacterial activity of the C-7 side chain of 3-aminoquinazolinediones. Bioorganic & Medicinal Chemistry Letters (2008)
• In Vitro and In Vivo Activities of PD 0305970 and PD 0326448, New Bacterial Gyrase/Topoisomerase Inhibitors with Potent Antibacterial Activities versus Multidrug-Resistant Gram-Positive and Fastidious Organism Groups. Antimicrobial Agents and Chemotherapy (2007)
• The synthesis and biological evaluation of novel series of nitrile-containing fluoroquinolones as antibacterial agents. Bioorganic & Medicinal Chemistry Letters (2007)
• Structure–activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors. Bioorganic & Medicinal Chemistry Letters (2007)
• 3-Aminoquinazolinediones as a New Class of Antibacterial Agents Demonstrating Excellent Antibacterial Activity Against Wild-Type and Multidrug Resistant Organisms. Journal of Medicinal Chemistry (2006-11-01)
• A facile synthesis of substituted 3-amino-1H-quinazoline-2,4-diones. Journal of Heterocyclic Chemistry (2005)
• Dicarbonylbis(triphenylphosphine)nickel(0). Encyclopedia of Reagents for Organic Synthesis (2001-04-15)
• Bromo(o-tolyl)bis(triethylphosphine)nickel(II). Encyclopedia of Reagents for Organic Synthesis (2001-04-15)
• Synthesis of the novel antibacterial 6,8-dihydroxy-7-propyl-9H-pyrrolo[1,2-b][1,3]-benzoxazin-9-one. Tetrahedron Letters (2000)
• 5,6-Dihydropyran-2-ones Possessing Various Sulfonyl Functionalities:  Potent Nonpeptidic Inhibitors of HIV Protease. Journal of Medicinal Chemistry (2000-03-01)
• Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor. Bioorganic & Medicinal Chemistry (1999)
• Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing a novel and achiral 3-(2-t-butyl-5-methyl-4-sulfamate)phenylthio moiety. Bioorganic & Medicinal Chemistry Letters (1999)
• 4-Hydroxy-5,6-Dihydro-2H-pyran-2-ones. 3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S1′ and S2′ of the HIV-1 protease enzyme. Bioorganic & Medicinal Chemistry Letters (1999)
• Nonpeptidic HIV protease inhibitors: 6-alkyl-5, 6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl, 5-methylphenyl thio) moiety: Antiviral activities and pharmacokinetic properties. Bioorganic & Medicinal Chemistry Letters (1999)
• Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydro-2-pyranones possessing a novel and achiral 3-(2-t-butyl-5-methyl-4-sulfamate)phenylthio moiety. Bioorganic & Medicinal Chemistry Letters (1999)
• Substituted salicylanilides as inhibitors of two-component regulatory systems in bacteria. Chemtracts (1999) (1999)
• 4-Hydroxy-5,6-dihydropyrones. 2. Potent Non-Peptide Inhibitors of HIV Protease. Journal of Medicinal Chemistry (1997-11-01)
• Synthesis of 5,6-Dihydro-4-hydroxy-2- pyrones as HIV-1 Protease Inhibitors:  The Profound Effect of Polarity on Antiviral Activity. Journal of Medicinal Chemistry (1997-11-01)
• Discovery and optimization of nonpeptide HIV-1 protease inhibitors. Bioorganic & Medicinal Chemistry (1996)
• Inhibitors of HIV protease: Unique non-peptide active site templates. Journal of Molecular Recognition (1996)
• A simple procedure for the synthesis of 3‐(substituted‐sulfanyl)‐4‐hydroxy‐6‐substituted‐pyran‐2‐ones. Journal of Heterocyclic Chemistry (1994)
• Hydrozirconation-transmetalation. A mild, direct route to higher order vinylic cuprates from monosubstituted acetylenes. Journal of the American Chemical Society (1990)
• On the composition of Yamamoto's reagent: "RCu.cntdot.BF3". Journal of the American Chemical Society (1990)
• Higher order cyanocuprates R2Cu(CN)Li2: discrete reagents or lower order lithium cyanide (LiCN) modified Gilman cuprates?. Journal of the American Chemical Society (1990)
• Ligand exchange between cyanocuprates and allylic stannanes: a novel, direct route to allylic cuprates possessing remarkable reactivity and stability. Journal of the American Chemical Society (1990)
• New methodology for conjugate additions of allylic ligands to .alpha.,.beta.-unsaturated ketones: synthetic and spectroscopic studies. Journal of the American Chemical Society (1990)
• A new method for the in situ generation of Cp2Zr(H)Cl (Schwartz' Reagent). Tetrahedron Letters (1990)
• Fine tuning the silicon-tin bond: transmetalations forming either trialkylstannyl or trialkylsilyl higher order cyanocuprates. The Journal of Organic Chemistry (1989)
• Understanding allylic organocuprates: .sigma.- or .pi.-bound reagents?. The Journal of Organic Chemistry (1989)
• Transmetalation reactions of higher order cyanocuprates: Direct formation of trialkyltin cuprates from tin hydrides which bypasses organolithium intermediates. Tetrahedron Letters (1989)
• The synthesis of β-Hydroxy-(E)-vinylstannanes using an “in-situ” generated cuprate reagent derived from (E)-bis-(tributylstannyl)ethylene. Tetrahedron Letters (1989)
• Effects of boron trifluoride etherate on higher order organocuprate reactions: substrate activation or cuprate modification?. Journal of the American Chemical Society (1988)
• Effects of gengenions on organocuprate reactivity/selectivity: Higher order, mixed lithio- cyanocuprates. Tetrahedron Letters (1988)
• Unexpected affects of Me3Si-X on reactions of higher order cyanocuprates. Tetrahedron Letters (1988)
• Design, Synthesis, and Biological Activity of Novel Ornithine Decarboxylase (ODC) Inhibitors. ()

Employment

• ZZ1Chief Technical Officer, ZZ2Tarn Biosciences ZZ3East Lansing ZZ$ (2021)
• ZZ1Research Professor, ZZ2Michigan State University ZZ3East Lansing ZZ$https://ror.org/05hs6h993 (2016-05-01)
• ZZ1VP of Development, ZZ2Akeila Bio ZZ3Ann Arbor ZZ$ (2021—2026)
• ZZ1Adjunct Professor, ZZ2Western Michigan University ZZ3Kalamazoo ZZ$https://ror.org/04j198w64 (2014—2015)
• ZZ1Associate Director / Associate Fellow, ZZ2Zoetis, Inc. ZZ3Kalamazoo ZZ$ (2013—2015)
• ZZ1Associate Director / Associate Research Fellow., ZZ2Pfizer ZZ3Zalamazoo ZZ$ (2007—2013)
• ZZ1Associate Research Fellow, ZZ2Pfizer ZZ3Ann Arbor ZZ$ (1992—2007)