Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102)

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (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.

In: ChemMedChem, Vol. 11, No. 4, 2016, p. 403-419.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Haym, I, Huynh, THV, Hansen, SW, Pedersen, MHF, Ruiz, JA, Erichsen, MN, Gynther, M, Bjørn-Yoshimoto, WE, Abrahamsen, B, Bastlund, JF, Bundgaard, C, Eriksen, AL, Jensen, AA & Bunch, L 2016, 'Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102)', ChemMedChem, vol. 11, no. 4, pp. 403-419. https://doi.org/10.1002/cmdc.201500527

APA

Haym, I., Huynh, T. H. V., Hansen, S. W., Pedersen, M. H. F., Ruiz, J. A., Erichsen, M. N., Gynther, M., Bjørn-Yoshimoto, W. E., Abrahamsen, B., Bastlund, J. F., Bundgaard, C., Eriksen, A. L., Jensen, A. A., & Bunch, L. (2016). Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102). ChemMedChem, 11(4), 403-419. https://doi.org/10.1002/cmdc.201500527

Vancouver

Haym I, Huynh THV, Hansen SW, Pedersen MHF, Ruiz JA, Erichsen MN et al. Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102). ChemMedChem. 2016;11(4):403-419. https://doi.org/10.1002/cmdc.201500527

Author

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. / Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102). In: ChemMedChem. 2016 ; Vol. 11, No. 4. pp. 403-419.

Bibtex

@article{5d2bb60415204cf2b81411e3322952bb,

title = "Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102)",

abstract = "Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood–brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg−1) of the closely related analogue UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 μm after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH-102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH-102 (10 μm) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH-102 (20 mg kg−1) did not induce acute effects or any visible changes in behavior.",

keywords = "Animals, Benzopyrans/adverse effects, Biological Availability, Brain/drug effects, Excitatory Amino Acid Transporter 1/antagonists & inhibitors, Humans, Locomotion/drug effects, Mice, Rats, Structure-Activity Relationship",

author = "Isabell Haym and Huynh, {Tri H V} and Hansen, {Stinne W} and Pedersen, {Martin H F} and Ruiz, {Josep A} and Erichsen, {Mette N} and Mikko Gynther and Bj{\o}rn-Yoshimoto, {Walden E} and Bjarke Abrahamsen and Bastlund, {Jesper F} and Christoffer Bundgaard and Eriksen, {Anette L} and Jensen, {Anders A} and Lennart Bunch",

note = "{\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2016",

doi = "10.1002/cmdc.201500527",

language = "English",

volume = "11",

pages = "403--419",

journal = "Farmaco",

issn = "1860-7179",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "4",

}

RIS

TY - JOUR

T1 - Bioavailability studies and in vitro profiling of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-102)

AU - Haym, Isabell

AU - Huynh, Tri H V

AU - Hansen, Stinne W

AU - Pedersen, Martin H F

AU - Ruiz, Josep A

AU - Erichsen, Mette N

AU - Gynther, Mikko

AU - Bjørn-Yoshimoto, Walden E

AU - Abrahamsen, Bjarke

AU - Bastlund, Jesper F

AU - Bundgaard, Christoffer

AU - Eriksen, Anette L

AU - Jensen, Anders A

AU - Bunch, Lennart

PY - 2016

Y1 - 2016

N2 - Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood–brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg−1) of the closely related analogue UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 μm after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH-102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH-102 (10 μm) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH-102 (20 mg kg−1) did not induce acute effects or any visible changes in behavior.

AB - Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood–brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg−1) of the closely related analogue UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 μm after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH-102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH-102 (10 μm) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH-102 (20 mg kg−1) did not induce acute effects or any visible changes in behavior.

KW - Animals

KW - Benzopyrans/adverse effects

KW - Biological Availability

KW - Brain/drug effects

KW - Excitatory Amino Acid Transporter 1/antagonists & inhibitors

KW - Humans

KW - Locomotion/drug effects

KW - Mice

KW - Rats

KW - Structure-Activity Relationship

U2 - 10.1002/cmdc.201500527

DO - 10.1002/cmdc.201500527

M3 - Journal article

C2 - 26797816

VL - 11

SP - 403

EP - 419

JO - Farmaco

JF - Farmaco

SN - 1860-7179

IS - 4

ER -

ID: 150772806