Research ArticleDrug Discovery and Translational Medicine
Open Access
Improved Inhibitory and Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADMET) Properties of Blebbistatin Derivatives Indicate That Blebbistatin Scaffold Is Ideal for drug Development Targeting Myosin-2
Máté Gyimesi, Anna Á. Rauscher, Sharad Kumar Suthar, Kamirán Á. Hamow, Kinga Oravecz, István Lőrincz, Zsolt Borhegyi, Máté T. Déri, Ádám F. Kiss, Katalin Monostory, Pál Tamás Szabó, Suman Nag, Ivan Tomasic, Jacob Krans, Patrick J. Tierney, Mihály Kovács, László Kornya and András Málnási-Csizmadia
Journal of Pharmacology and Experimental Therapeutics March 2021, 376 (3) 358-373; DOI: https://doi.org/10.1124/jpet.120.000167
Máté Gyimesi
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Anna Á. Rauscher
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Sharad Kumar Suthar
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Kamirán Á. Hamow
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Kinga Oravecz
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
István Lőrincz
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Zsolt Borhegyi
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Máté T. Déri
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Ádám F. Kiss
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Katalin Monostory
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Pál Tamás Szabó
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Suman Nag
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Ivan Tomasic
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Jacob Krans
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Patrick J. Tierney
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
Mihály Kovács
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
László Kornya
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
András Málnási-Csizmadia
Department of Biochemistry, Eötvös Loránd University, Budapest and Martonvásár, Hungary (M.G., K.O., I.L., Z.B., M.K., A.M.-C.); MTA-ELTE Motor Pharmacology Research Group, Budapest, Hungary (M.G., M.K., A.M.-C.); Motorharma Ltd., Budapest, Hungary (A.Á.R.); Printnet Ltd., Budapest, Hungary (S.K.S., I.L.); Plant Protection Institute, Centre for Agricultural Research, Martonvásár, Hungary (K.Á.H.); Metabolic Drug Interactions Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary (M.T.D., Á.F.K., K.M.); Research Centre for Natural Sciences, Instrumentation Center, MS Metabolomic Research Laboratory, Budapest, Hungary (P.T.S.); Department of Biology, MyoKardia Inc., Brisbane, California (S.N., I.T.); Department of Neuroscience, Western New England University, Springfield, Massachusetts (J.K., P.J.T.); and Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary (L.K.)
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Research ArticleDrug Discovery and Translational Medicine
Blebbistatin Scaffold Is Ideal for Drug Development
Máté Gyimesi, Anna Á. Rauscher, Sharad Kumar Suthar, Kamirán Á. Hamow, Kinga Oravecz, István Lőrincz, Zsolt Borhegyi, Máté T. Déri, Ádám F. Kiss, Katalin Monostory, Pál Tamás Szabó, Suman Nag, Ivan Tomasic, Jacob Krans, Patrick J. Tierney, Mihály Kovács, László Kornya and András Málnási-Csizmadia
Journal of Pharmacology and Experimental Therapeutics March 1, 2021, 376 (3) 358-373; DOI: https://doi.org/10.1124/jpet.120.000167
Research ArticleDrug Discovery and Translational Medicine
Blebbistatin Scaffold Is Ideal for Drug Development
Máté Gyimesi, Anna Á. Rauscher, Sharad Kumar Suthar, Kamirán Á. Hamow, Kinga Oravecz, István Lőrincz, Zsolt Borhegyi, Máté T. Déri, Ádám F. Kiss, Katalin Monostory, Pál Tamás Szabó, Suman Nag, Ivan Tomasic, Jacob Krans, Patrick J. Tierney, Mihály Kovács, László Kornya and András Málnási-Csizmadia
Journal of Pharmacology and Experimental Therapeutics March 1, 2021, 376 (3) 358-373; DOI: https://doi.org/10.1124/jpet.120.000167
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