ArticleThe Journal of pharmacology and experimental therapeutics2021
Identification and Characterization of Two Structurally Related Dipeptides that Enhance Catalytic Efficiency of Neurolysin.
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Article in The Journal of pharmacology and experimental therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Structural and functional dissection of human neurolysin through alanine-scanning mutagenesis.The FEBS journal · 2026Article
- Discovery of a pyridine-piperazine-based small molecule that enhances the activity of peptidase neurolysin.The Journal of pharmacology and experimental therapeutics · 2026Article
- Conformation Driven Enhancement of Neurolysin Activity in Presence of a Small Molecule Activator.bioRxiv : the preprint server for biology · 2026Article
- The Missing Enzymes: A Call to Update Pharmacological Profiling Practices for Better Drug Safety Assessment.Journal of medicinal chemistry · 2025Review
- Structural basis of divergent substrate recognition and inhibition of human neurolysin.Scientific reports · 2024Article
- Imidazole Bioisostere Activators of Endopeptidase Neurolysin with Enhanced Potency and Metabolic Stability.ACS medicinal chemistry letters · 2024Article
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- Discovery of the Next Generation of Non-peptidomimetic Neurolysin Activators with High Blood-Brain Barrier Permeability: a Pharmacokinetics Study in Healthy and Stroke Animals.Pharmaceutical research · 2023Article
- Is Diminazene an Angiotensin-Converting Enzyme 2 (ACE2) Activator? Experimental Evidence and Implications.The Journal of pharmacology and experimental therapeutics · 2022Article
- Structure-activity relationship studies of functionalized aromatic peptidomimetics as neurolysin activators.Bioorganic & medicinal chemistry letters · 2022Article
- Small molecule neurolysin activators, potential multi-mechanism agents for ischemic stroke therapy.Expert opinion on therapeutic targets · 2022Article
- Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability.Journal of medicinal chemistry · 2021Article
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Authors and funding
12 authors at 6 institutions in 1 country.
Srinidhi JayaramanDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Joanna KocotDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Shiva Hadi EsfahaniDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Naomi J WanglerDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Arzu UyarDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Yehia MechrefDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Paul C TrippierDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Thomas J AbbruscatoDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Alex DicksonDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Hideki AiharaDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
David A OstrovDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.).
Vardan T KaramyanDepartment of Pharmaceutical Sciences (S.J., J.K., S.H.E., N.J.W., T.J.A., V.T.K.) and Center for Blood Brain Barrier Research (T.J.A., V.T.K.), School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan (A.U., A.D.); Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas (Y.M.); Department of Pharmaceutical Sciences, College of Pharmacy and Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska (P.C.T.); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota (H.A.); and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida (D.A.O.) vardan.karamyan@ttuhsc.edu.
Michigan State University · USUniversity of Minnesota · USUniversity of Florida · USTexas Tech University · USTexas Tech University Health Sciences Center · USUniversity of Nebraska Medical Center · US
Funding
Structural studies of viral replication and invasionR35GM118047 · NIGMS · UNIVERSITY OF MINNESOTA · PI Hideki Aihara · 2016 to 2026
$6.3MDevelopment and Characterization of Small Molecule Activators of Peptidase Neurolysin for Stroke TherapyR01NS106879 · NINDS · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI Thomas J Abbruscato, Vardan T. Karamyan · 2018 to 2026
$4.2MNIGMS NIH HHS R35 GM118047NINDS NIH HHS R01 NS106879
Abstract
Neurolysin (Nln) is a recently recognized endogenous mechanism functioning to preserve the brain from ischemic injury. To further understand the pathophysiological function of this peptidase in stroke and other neurologic disorders, the present study was designed to identify small molecule activators of Nln. Using a computational approach, the structure of Nln was explored, which was followed by docking and in silico screening of ∼140,000 molecules from the National Cancer Institute Developmental Therapeutics Program database. Top ranking compounds were evaluated in an Nln enzymatic assay, and two hit histidine-dipeptides were further studied in detail. The identified dipeptides enhanced the rate of synthetic substrate hydrolysis by recombinant (human and rat) and mouse brain-purified Nln in a concentration-dependent manner (micromolar A
Indexed as
AnimalsCatalysisDipeptidesDose-Response Relationship, DrugDrug SynergismHumansMetalloendopeptidasesMiceMolecular Docking SimulationProtein Structure, SecondaryProtein Structure, TertiaryRatsDipeptidesMetalloendopeptidasesneurolysin
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.