Mikko Gynther

Sex-specific changes in protein expression of membrane transporters in the brain cortex of 5xFAD mouse model of Alzheimer’s disease

Puris, Elena; Saveleva, Liudmila; Auriola, Seppo; Gynther, Mikko; Kanninen, Katja M; Fricker, Gert. 2024. Frontiers in pharmacology. 15: . 1365051

In vitro identification of decreased function phenotype ABCG2 variants

Suominen, Laura; Sjöstedt, Noora; Vellonen, Kati-Sisko; Gynther, Mikko; Auriola, Seppo; Kidron, Heidi. 2023. European journal of pharmaceutical sciences. 188:

Metabolomic, Lipidomic and Proteomic Characterisation of Lipopolysaccharide-induced Inflammation Mouse Model

Puris, Elena; Kouřil, Štěpán; Najdekr, Lukáš; Auriola, Seppo; Loppi, Sanna; Korhonen, Paula; Gómez-Budia, Mireia; Fricker, Gert; Kanninen, Katja M; Malm, Tarja; Friedecký, David; Gynther, Mikko. 2022. Neuroscience. 496: 165-178

Systemic inflammation elevates cytosolic prolyl oligopeptidase protein expression but not peptidase activity in the cerebral cortices of familial Alzheimer`s disease modeling mice

Puris, Elena; Jalkanen, Aaro; Auriola, Seppo; Loppi, Sanna; Korhonen, Paula; Kanninen, Katja M.; Malm, Tarja; Koistinaho, Jari; Gynther, Mikko. 2022. Brain disorders. 6:

L-Type Amino Acid Transporter 1-Utilizing Prodrugs of Ketoprofen Can Efficiently Reduce Brain Prostaglandin Levels

Montaser, Ahmed; Lehtonen, Marko; Gynther, Mikko; Huttunen, Kristiina. 2020. Pharmaceutics. 12: 344

L-Type amino acid transporter 1 as a target for drug delivery

Puris, Elena; Gynther, Mikko; Auriola, Seppo; Huttunen, Kristiina. 2020. Pharmaceutical research. 37: 88

L-Type Amino Acid Transporter 1 (LAT1)-Utilizing Prodrugs Are Carrier-Selective Despite Having Low Affinity for Organic Anion Transporting Polypeptides (OATPs)

Huttunen, Johanna; Gynther, Mikko; Vellonen, KatiSisko; Huttunen, Kristiina M. 2019. International journal of pharmaceutics. 571: 118714

L-Type Amino Acid Transporter 1 (LAT1/Lat1)-Utilizing Prodrugs Can Improve the Delivery of Drugs into Neurons, Astrocytes and Microglia

Huttunen J, Peltokangas S, Gynther M, Natunen T, Hiltunen M, Auriola S, Ruponen M, Vellonen KS, Huttunen KM. 2019. Scientific reports. 9: 12860

L-type amino acid transporter 1 utilizing prodrugs of ferulic acid revealed structural features supporting the design of prodrugs for brain delivery

Puris, E; Gynther, M; Huttunen, J; Auriola, S; Huttunen, KM. 2019. European journal of pharmaceutical sciences. 129: 99-109

Laparoscopic Roux-en-Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates

Puris, E; Pasanen, M; Ranta, VP; Gynther, M; Petsalo, A; Käkelä, P; Männistö, V; Pihlajamäki, J. 2019. Basic and clinical pharmacology and toxicology. 125: 123-132

Mechanistic Study on the Use of the l-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets

Puris, Elena; Gynther, Mikko; de Lange, Elizabeth C M; Auriola, Seppo; Harnmarlund-Udenaes, Margareta; Huttunen, Kristiina M; Loryan, Irena. 2019. Molecular pharmaceutics. 16: 3261-3274

Sleep-State Dependent Alterations in Brain Functional Connectivity under Urethane Anesthesia in a Rat Model of Early-Stage Parkinson's Disease

Zhurakovskaya, Ekaterina; Leikas, Juuso; Pirttimäki, Tiina; Casas Mon, Francesc; Gynther, Mikko; Aliev, Rubin; Rantamäki, Tomi; Tanila, Heikki; Forsberg, Markus M; Gröhn, Olli; Paasonen, Jaakko; Jalkanen, Aaro J. 2019. eNeuro. 6: 1-12

(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands : Further Exploration of Bioisosteric Replacements and Structural and Biological Investigation

Brogi, Simone; Brindisi, Margherita; Butini, Stefania; Kshirsagar, Giridhar U.; Maramai, Samuele; Chemi, Giulia; Gemma, Sandra; Campiani, Giuseppe; Novellino, Ettore; Fiorenzani, Paolo; Pinassi, Jessica; Alois, Anna Maria; Gynther, Mikko; Venskutonyte, Raminta; Han, Liwei; Frydenvang, Karla; Kastrup, Jette Sandholm; Pickering, Darryl S. 2018. Journal of medicinal chemistry. 61: 2124-2130

Alzheimer's Disease Phenotype or Inflammatory Insult Does Not Alter Function of L-Type Amino Acid Transporter 1 in Mouse Blood-Brain Barrier and Primary Astrocytes

Gynther, Mikko; Puris, Elena; Peltokangas, Soile; Auriola, Seppo; Kanninen, Katja M; Koistinaho, Jari; Huttunen, Kristiina M; Ruponen, Marika; Vellonen, Kati-Sisko. 2018. Pharmaceutical research. 2019; 36: 17

Extracellular Prolyl Oligopeptidase Derived from Activated Microglia is a Potential Neuroprotection Target.

Natunen, Teemu A; Gynther, Mikko; Rostalski, Hannah; Jaako, Külli; Jalkanen, Aaro J. 2018. Basic and clinical pharmacology and toxicology. 2019; 124: 40-49

Structural properties for selective and efficient L-type amino acid transporter 1 (LAT1) mediated cellular uptake

Kärkkäinen, J; Gynther, M; Kokkola, T; Petsalo, A; Auriola, S; Lahtela-Kakkonen, M; Laine, K; Rautio, J; Huttunen, KM. 2018. International journal of pharmaceutics. 544: 91-99

Targeted efflux transporter inhibitors - a solution to improve poor cellular accumulation of anti-cancer agents

Huttunen, J; Gynther, M; Huttunen, KM. 2018. International journal of pharmaceutics. 550: 278-289

Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist

Gynther M, Proietti Silvestri I, Hansen JC, Hansen KB, Malm T, Ishchenko Y, Larsen Y, Han L, Kayser S, Auriola S, Petsalo A, Nielsen B, Pickering DS, Bunch L. 2017. Journal of medicinal chemistry. 60: 9885-9904

Disease-Induced Alterations in Brain Drug Transporters in Animal Models of Alzheimer's Disease

Vellonen KS, Ihalainen J, Boucau M-C, Gosselet F, Picardat T, Gynther M, Kanninen KM, White AR, Malm T, Koistinaho J, Forsberg MM, Ruponen M. 2017. Pharmaceutical research. 34: 2652-2662

Effects of Dimeric PSD-95 Inhibition on Excitotoxic Cell Death and Outcome After Controlled Cortical Impact in Rats

Sommer JB, Bach A, Malá H, Gynther M, Bjerre AS, Gram MG, Marschner L, Strømgaard K, Mogensen J, Pickering DS. 2017. Neurochemical research. 42: 3401-3413

L-type amino acid transporter 1 utilizing prodrugs : how to achieve effective brain delivery and low systemic exposure of drugs

Puris E, Gynther M, Huttunen J, Petsalo A, Huttunen KM. 2017. Journal of controlled release. 261: 93-104

A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells

Huttunen Kristiina M, Gynther Mikko, Huttunen Johanna, Puris Elena, Spicer Julie A, Denny William A. 2016. Journal of medicinal chemistry. 59: 5740-5751

A liquid chromatography-tandem mass spectrometry analysis of nine cytochrome P450 probe drugs and their corresponding metabolites in human serum and urine

Puris Elena, Pasanen Markku, Gynther Mikko, Häkkinen Merja R, Pihlajamäki Jussi, Keränen Tapani, Honkakoski Paavo, Raunio Hannu, Petsalo Aleksanteri. 2016. Analytical and bioanalytical chemistry. 2017; 409: 251-268

Amino Acid Promoieties Alter Valproic Acid Pharmacokinetics and Enable Extended Brain Exposure

Gynther Mikko, Peura Lauri, Vernerová Monika, Leppänen Jukka, Kärkkäinen Jussi, Lehtonen Marko, Rautio Jarkko, Huttunen Kristiina M. 2016. Neurochemical research. 41: 2797-2809

Bioavailability Studies and in vitro Profiling of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor UCPH-102

Haym Isabell, Huynh Tri H V, Hansen Stinne W, Pedersen Martin H F, Ruiz Josep A, Erichsen Mette N, Gynther Mikko, Bjørn-Yoshimoto Walden E, Abrahamsen Bjarke, Bastlund Jesper F, Bundgaard Christoffer, Eriksen Anette L, Jensen Anders A, Bunch Lennart. 2016. Chemmedchem. 11: 403-419

Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain, cognition and motor function

Andreasen Jesper T, Nasser Arafat, Caballero-Puntiverio Maitane, Sahlholt Maj, Bach Anders, Gynther Mikko, Strømgaard Kristian, Pickering Darryl S. 2016. European journal of pharmacology. 780: 166-173

In vivo characterization of the ultrapotent monoacylglycerol lipase inhibitor {4-[bis-(benzo[d][1,3]dioxol-5-yl)methyl]-piperidin-1-yl} (1H-1,2,4-triazol-1-yl)methanone (JJKK-048)

Aaltonen Niina, Kedzierska Ewa, Orzelska-Gorka Jolanta, Lehtonen Marko, Navia-Paldanius Dina, Jakupovic Hermina, Savinainen Juha, Nevalainen Tapio, Laitinen Jarmo T, Parkkari Teija, Gynther Mikko. 2016. Journal of pharmacology and experimental therapeutics. 359: 62-72

Systemic and Brain Pharmacokinetics of Perforin Inhibitor Prodrugs

Gynther Mikko, Pickering Darryl S, Spicer Julie A, Denny William A, Huttunen Kristiina M. 2016. Molecular pharmaceutics. 13: 2484-2491

L-type Amino Acid Transporter 1 (LAT1)-Mediated Targeted Delivery of Perforin Inhibitors

Huttunen Kristiina M, Huttunen Johanna, Aufderhaar Imke, Gynther Mikko, Denny William A, Spicer Julie A. 2015. International journal of pharmaceutics. 498 (2016): 205-216

Aihiolääketeknologia lääkekehityksessä

Rautio Jarkko, Huttunen Kristiina, Gynther Mikko, Laine Krista, Leppänen Jukka, Kärkkäinen Jussi, Malmioja Kalle. 2014. Dosis. 30: 209

Amino acid ester prodrugs conjugated to the alpha-carboxylic acid group do not display affinity for the L-type amino acid transporter 1 (LAT1)

Rautio Jarkko, Kärkkäinen Jussi, Huttunen Kristiina, Gynther Mikko. 2014. European journal of pharmaceutical sciences. 2015; 66: 36-40

Blood-brain barrier permeability and brain uptake mechanism of kainic acid and dihydrokainic acid

Gynther Mikko, Petsalo Aleksanteri, Hansen Steen H, Bunch Lennart, Pickering Darryl S. 2014. Neurochemical research. 2015; 40: 542-549

Brain Pharmacokinetics of Ganciclovir in Rats with Orthotopic BT4C Glioma

Gynther Mikko, Kääriäinen Tiina M, Hakkarainen Jenni J, Jalkanen Aaro J, Petsalo Aleksanteri, Lehtonen Marko, Peura Lauri, Kurkipuro Jere, Samaranayake Haritha, Yla-Herttuala Seppo, Rautio Jarkko, Forsberg Markus M. 2014. Drug metabolism and disposition. 2015; 43: 140-146

Evaluation of novel imidazotetrazine analogues designed to overcome temozolomide resistance and glioblastoma regrowth

Ramirez Yulian P, Mladek Ann C, Phillips Roger M, Gynther Mikko, Rautio Jarkko, Ross Alonzo H, Wheelhouse Richard T, Sakaria Jann N. 2014. Molecular cancer therapeutics. 2015; 14: 111-119

Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors

Patel Jayendra Z, Nevalainen Tapio J, Savinainen Juha R, Adams Yahaya, Laitinen Tuomo, Runyon Robert S, Vaara Miia, Ahenkorah Stephen, Kaczor Agnieszka A, Navia-Paldanius Dina, Gynther Mikko, Aaltonen Niina, Joharapurkar Amit A, Jain Mukul R, Haka Abigail S, Maxfield Frederick R, Laitinen Jarmo T, Parkkari Teija. 2014. Chemmedchem. 2015; 10: 253-265

Quantitative Insight into the Design of Compounds Recognized by the L-Type Amino Acid Transporter 1 (LAT1)

Ylikangas Henna, Malmioja Kalle, Peura Lauri, Gynther Mikko, Nwachukwu Emmanuel O, Leppänen Jukka, Laine Krista, Rautio Jarkko, Lahtela-Kakkonen Maija, Huttunen Kristiina M, Poso Antti. 2014. Chemmedchem. 9: 2699-2707

Design, synthesis and brain uptake of LAT1-targeted amino acid prodrugs of dopamine

Peura Lauri, Malmioja Kalle, Huttunen Kristiina, Leppänen Jukka, Hämäläinen Miia, Forsberg Markus M, Gynther Mikko, Rautio Jarkko, Laine Krista. 2013. Pharmaceutical research. 30: 2523-2537

Does increasing the ratio of AMPA-to-NMDA receptor mediated neurotransmission engender antidepressant action? Studies in the mouse forced swim and tail suspension tests

Andreasen JT, Gynther M, Rygaard A, Bøgelund T, Nielsen SD, Clausen RP, Mogensen J, Pickering DS. 2013. Neuroscience letters. 546: 6-10

LAT1-mediated prodrug uptake: a way to breach the blood-brain barrier?

Rautio Jarkko, Gynther Mikko, Laine Krista. 2013. Therapeutic delivery. 4: 281-284

UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK-801

Andreasen Jesper T, Bach Anders, Gynther Mikko, Nasser Arafat, Mogensen Jesper, Strømgaard Kristian, Pickering Darryl S. 2013. Neuropharmacology. 67: 193-200

Large amino acid transporter 1 (LAT1) prodrugs of valproic acid: new prodrug design ideas for central nervous system delivery

Peura Lauri, Malmioja Kalle, Laine Krista, Leppänen Jukka, Gynther Mikko, Isotalo Antti, Rautio Jarkko. 2011. Molecular pharmaceutics. 8: 1857-1866

New Prodrug Design Ideas for Transporter-Mediated CNS Drug Delivery

Kalle Malmioja, Lauri Peura, Krista Laine, Jukka Leppänen, Mikko Gynther, Jarkko Rautio. 2011.

New Prodrug Desing Ideas for Large Amino Acid Transporter 1 -Mediated Drug Brain Delivery

Peura L, Malmioja K, Laine K, Leppänen J, Gynther M & Rautio J. 2011.

Blood-Brain Barrier Transporters in CNS Drug Delivery: Design and Biological Evaluation of LAT1 and GluT1 -Targeted Prodrugs

Gynther Mikko. 2010. Publications of the University of Eastern Finland. Dissertations in Health Sciences

Brain uptake of ketoprofen-lysine prodrug in rats

Gynther M, Jalkanen A, Lehtonen M, Forsberg M, Laine K, Ropponen J, Leppänen J, Knuuti J & Rautio J. 2010. International journal of pharmaceutics. 399: 121-128

Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats

Gynther M, Ropponen J, Laine K, Leppänen J, Haapakoski P, Peura L, Järvinen T, Rautio J. 2009. Journal of medicinal chemistry. 52: 3348-3353

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Research groups

Sex-specific changes in protein expression of membrane transporters in the brain cortex of 5xFAD mouse model of Alzheimer’s disease

In vitro identification of decreased function phenotype ABCG2 variants

Metabolomic, Lipidomic and Proteomic Characterisation of Lipopolysaccharide-induced Inflammation Mouse Model

Systemic inflammation elevates cytosolic prolyl oligopeptidase protein expression but not peptidase activity in the cerebral cortices of familial Alzheimer`s disease modeling mice

L-Type Amino Acid Transporter 1-Utilizing Prodrugs of Ketoprofen Can Efficiently Reduce Brain Prostaglandin Levels

L-Type amino acid transporter 1 as a target for drug delivery

L-Type Amino Acid Transporter 1 (LAT1)-Utilizing Prodrugs Are Carrier-Selective Despite Having Low Affinity for Organic Anion Transporting Polypeptides (OATPs)

L-Type Amino Acid Transporter 1 (LAT1/Lat1)-Utilizing Prodrugs Can Improve the Delivery of Drugs into Neurons, Astrocytes and Microglia

L-type amino acid transporter 1 utilizing prodrugs of ferulic acid revealed structural features supporting the design of prodrugs for brain delivery

Laparoscopic Roux-en-Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates

Mechanistic Study on the Use of the l-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets

Sleep-State Dependent Alterations in Brain Functional Connectivity under Urethane Anesthesia in a Rat Model of Early-Stage Parkinson's Disease

(S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands : Further Exploration of Bioisosteric Replacements and Structural and Biological Investigation

Alzheimer's Disease Phenotype or Inflammatory Insult Does Not Alter Function of L-Type Amino Acid Transporter 1 in Mouse Blood-Brain Barrier and Primary Astrocytes

Extracellular Prolyl Oligopeptidase Derived from Activated Microglia is a Potential Neuroprotection Target.

Structural properties for selective and efficient L-type amino acid transporter 1 (LAT1) mediated cellular uptake

Targeted efflux transporter inhibitors - a solution to improve poor cellular accumulation of anti-cancer agents

Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist

Disease-Induced Alterations in Brain Drug Transporters in Animal Models of Alzheimer's Disease

Effects of Dimeric PSD-95 Inhibition on Excitotoxic Cell Death and Outcome After Controlled Cortical Impact in Rats

L-type amino acid transporter 1 utilizing prodrugs : how to achieve effective brain delivery and low systemic exposure of drugs

A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells

A liquid chromatography-tandem mass spectrometry analysis of nine cytochrome P450 probe drugs and their corresponding metabolites in human serum and urine

Amino Acid Promoieties Alter Valproic Acid Pharmacokinetics and Enable Extended Brain Exposure

Bioavailability Studies and in vitro Profiling of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor UCPH-102

Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain, cognition and motor function

In vivo characterization of the ultrapotent monoacylglycerol lipase inhibitor {4-[bis-(benzo[d][1,3]dioxol-5-yl)methyl]-piperidin-1-yl} (1H-1,2,4-triazol-1-yl)methanone (JJKK-048)

Systemic and Brain Pharmacokinetics of Perforin Inhibitor Prodrugs

L-type Amino Acid Transporter 1 (LAT1)-Mediated Targeted Delivery of Perforin Inhibitors

Aihiolääketeknologia lääkekehityksessä

Amino acid ester prodrugs conjugated to the alpha-carboxylic acid group do not display affinity for the L-type amino acid transporter 1 (LAT1)

Blood-brain barrier permeability and brain uptake mechanism of kainic acid and dihydrokainic acid

Brain Pharmacokinetics of Ganciclovir in Rats with Orthotopic BT4C Glioma

Evaluation of novel imidazotetrazine analogues designed to overcome temozolomide resistance and glioblastoma regrowth

Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors

Quantitative Insight into the Design of Compounds Recognized by the L-Type Amino Acid Transporter 1 (LAT1)

Design, synthesis and brain uptake of LAT1-targeted amino acid prodrugs of dopamine

Does increasing the ratio of AMPA-to-NMDA receptor mediated neurotransmission engender antidepressant action? Studies in the mouse forced swim and tail suspension tests

LAT1-mediated prodrug uptake: a way to breach the blood-brain barrier?

UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: comparison with the NMDA receptor antagonist MK-801

Large amino acid transporter 1 (LAT1) prodrugs of valproic acid: new prodrug design ideas for central nervous system delivery

New Prodrug Design Ideas for Transporter-Mediated CNS Drug Delivery

New Prodrug Desing Ideas for Large Amino Acid Transporter 1 -Mediated Drug Brain Delivery

Blood-Brain Barrier Transporters in CNS Drug Delivery: Design and Biological Evaluation of LAT1 and GluT1 -Targeted Prodrugs

Brain uptake of ketoprofen-lysine prodrug in rats

Glucose promoiety enables glucose transporter mediated brain uptake of ketoprofen and indomethacin prodrugs in rats

Enhanced brain drug delivery and targeting

Large neutral amino acid transporter enables brain drug delivery via prodrugs

Prodrug approaches for CNS delivery