Development of Non-GAT1-Selective Inhibitors: Challenges and Achievements
Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review
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Development of Non-GAT1-Selective Inhibitors : Challenges and Achievements. / Damgaard, Maria; Haugaard, Anne Stæhr; Kickinger, Stefanie; Al-Khawaja, Anas; Lie, Maria E K; Ecker, Gerhard F; Clausen, Rasmus Prætorius; Frølund, Bente.
Advances in Neurobiology. Vol. 16 Springer, 2017. p. 315-332 (Advances in Neurobiology).Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review
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TY - CHAP
T1 - Development of Non-GAT1-Selective Inhibitors
T2 - Challenges and Achievements
AU - Damgaard, Maria
AU - Haugaard, Anne Stæhr
AU - Kickinger, Stefanie
AU - Al-Khawaja, Anas
AU - Lie, Maria E K
AU - Ecker, Gerhard F
AU - Clausen, Rasmus Prætorius
AU - Frølund, Bente
PY - 2017
Y1 - 2017
N2 - γ-Aminobutyric acid (GABA) neurotransmission is terminated by the GABA transporters (GATs) via uptake of GABA into neurons and surrounding glial cells. Four different transporters have been identified: GAT1, GAT2, GAT3, and the betaine/GABA transporter 1 (BGT1). The GAT1 subtype is the most explored transporter due to its high abundance in the brain and the existence of selective and potent GAT1 inhibitors. Consequently, less is known about the role and therapeutic potential of the non-GAT1 subtypes. Emerging pharmacological evidence suggests that some of these transporters pose interesting targets in several brain disorders. Pharmacological non-GAT1-selective tool compounds are important to further investigate the involvement of GATs in different pathological conditions. Extensive medicinal chemistry efforts have been put into the development of subtype-selective inhibitors, but truly selective and potent inhibitors of non-GAT1 subtypes are still limited. This review covers the advances within the medicinal chemistry area and the structural basis for obtaining non-GAT1-selective inhibitors.
AB - γ-Aminobutyric acid (GABA) neurotransmission is terminated by the GABA transporters (GATs) via uptake of GABA into neurons and surrounding glial cells. Four different transporters have been identified: GAT1, GAT2, GAT3, and the betaine/GABA transporter 1 (BGT1). The GAT1 subtype is the most explored transporter due to its high abundance in the brain and the existence of selective and potent GAT1 inhibitors. Consequently, less is known about the role and therapeutic potential of the non-GAT1 subtypes. Emerging pharmacological evidence suggests that some of these transporters pose interesting targets in several brain disorders. Pharmacological non-GAT1-selective tool compounds are important to further investigate the involvement of GATs in different pathological conditions. Extensive medicinal chemistry efforts have been put into the development of subtype-selective inhibitors, but truly selective and potent inhibitors of non-GAT1 subtypes are still limited. This review covers the advances within the medicinal chemistry area and the structural basis for obtaining non-GAT1-selective inhibitors.
KW - Journal Article
U2 - 10.1007/978-3-319-55769-4_16
DO - 10.1007/978-3-319-55769-4_16
M3 - Book chapter
C2 - 28828618
VL - 16
T3 - Advances in Neurobiology
SP - 315
EP - 332
BT - Advances in Neurobiology
PB - Springer
ER -
ID: 186087055