Glycine reuptake inhibitor
ALX-1393[1]
Names
IUPAC name
(2S )-2-Amino-3-[(3-fluorophenyl)-(2-phenylmethoxyphenyl)methoxy]propanoic acid
Identifiers
ChEMBL
ChemSpider
InChI=1S/C23H22FNO4/c24-18-10-6-9-17(13-18)22(29-15-20(25)23(26)27)19-11-4-5-12-21(19)28-14-16-7-2-1-3-8-16/h1-13,20,22H,14-15,25H2,(H,26,27)/t20-,22?/m0/s1
Key: ADUSZEGHFWRTQS-AIBWNMTMSA-N
C1=CC=C(C=C1)COC2=CC=CC=C2C(C3=CC(=CC=C3)F)OCC(C(=O)O)N
Properties
C 23 H 22 F N O 4
Molar mass
−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
ALX-1393 is a glycine reuptake inhibitor .
Pharmacodynamics [ edit ] ALX-1393 works by inhibiting the action of GLYT2 .[2]
Potential uses [ edit ] ALX-1393 has been shown to have potential as an analgesic . This is thought to be due to the elevated glycine levels reducing the transmission of the pain signals.[3]
Tests have shown that it was able to help reduce cancer pain in a potent way.[4]
References [ edit ]
^ "(2S)-2-amino-3-{[2-(benzyloxy)phenyl](3-fluorophenyl)methoxy}propanoic acid" .^ Eckle, V.-S.; Antkowiak, B. (2013-12-03). "ALX 1393 inhibits spontaneous network activity by inducing glycinergic tonic currents in the spinal ventral horn" . Neuroscience . 253 : 165–171. doi :10.1016/j.neuroscience.2013.08.042 . ISSN 1873-7544 . PMID 23994185 . S2CID 30039776 . ^ Benito-Muñoz, Cristina; Perona, Almudena; Felipe, Raquel; Pérez-Siles, Gonzalo; Núñez, Enrique; Aragón, Carmen; López-Corcuera, Beatriz (2021-06-02). "Structural Determinants of the Neuronal Glycine Transporter 2 for the Selective Inhibitors ALX1393 and ORG25543" . ACS Chemical Neuroscience . 12 (11): 1860–1872. doi :10.1021/acschemneuro.0c00602 . ISSN 1948-7193 . PMC 8691691 PMID 34003005 . ^ Motoyama, Naoyo; Morita, Katsuya; Shiraishi, Seiji; Kitayama, Tomoya; Kanematsu, Takashi; Uezono, Yasuhito; Dohi, Toshihiro (October 2014). "Relief of cancer pain by glycine transporter inhibitors" . Anesthesia and Analgesia . 119 (4): 988–995. doi :10.1213/ANE.0000000000000388 . ISSN 1526-7598 . PMID 25076101 .
Receptor (ligands )
GlyR Tooltip Glycine receptor
Positive modulators: Alcohols (e.g., brometone , chlorobutanol (chloretone) , ethanol (alcohol) , tert -butanol (2M2P)tribromoethanol , trichloroethanol , trifluoroethanol )Alkylbenzene sulfonate Anandamide Barbiturates (e.g., pentobarbital , sodium thiopental )Chlormethiazole D12-116 Dihydropyridines (e.g., nicardipine )Etomidate Ginseng constituents (e.g., ginsenosides (e.g., ginsenoside-Rf ))Glutamic acid (glutamate) Ivermectin Ketamine Neuroactive steroids (e.g., alfaxolone , pregnenolone (eltanolone) , pregnenolone acetate , minaxolone , ORG-20599 )Nitrous oxide Penicillin G Propofol Tamoxifen Tetrahydrocannabinol Triclofos Tropeines (e.g., atropine , bemesetron , cocaine , LY-278584 , tropisetron , zatosetron )Volatiles /gases (e.g., chloral hydrate , chloroform , desflurane , diethyl ether (ether) , enflurane , halothane , isoflurane , methoxyflurane , sevoflurane , toluene , trichloroethane (methyl chloroform) , trichloroethylene )Xenon Zinc Antagonists: 2-Aminostrychnine 2-Nitrostrychnine 4-Phenyl-4-formyl-N-methylpiperidine αEMBTL Bicuculline Brucine Cacotheline Caffeine Colchicine Colubrine Cyanotriphenylborate Dendrobine Diaboline Endocannabinoids (e.g., 2-AG , anandamide (AEA) )Gaboxadol (THIP) Gelsemine iso-THAZ Isobutyric acid Isonipecotic acid Isostrychnine Laudanosine N-Methylbicuculline N-Methylstrychnine N,N-Dimethylmuscimol Nipecotic acid Pitrazepin Pseudostrychnine Quinolines (e.g., 4-hydroxyquinoline , 4-hydroxyquinoline-3-carboxylic acid , 5,7-CIQA , 7-CIQ , 7-TFQ , 7-TFQA )RU-5135 Sinomenine Strychnine Thiocolchicoside Tutin Negative modulators: Amiloride Benzodiazepines (e.g., bromazepam , clonazepam , diazepam , flunitrazepam , flurazepam )Corymine Cyanotriphenylborate Daidzein Dihydropyridines (e.g., nicardipine , nifedipine , nitrendipine )Furosemide Genistein Ginkgo constituents (e.g., bilobalide , ginkgolides (e.g., ginkgolide A , ginkgolide B , ginkgolide C , ginkgolide J , ginkgolide M ))Imipramine NBQX Neuroactive steroids (e.g., 3α-androsterone sulfate , 3β-androsterone sulfate , deoxycorticosterone , DHEA sulfate , pregnenolone sulfate , progesterone )Opioids (e.g., codeine , dextromethorphan , dextrorphan , levomethadone , levorphanol , morphine , oripavine , pethidine , thebaine )Picrotoxin (i.e., picrotin and picrotoxinin )PMBA Riluzole Tropeines (e.g., bemesetron , LY-278584 , tropisetron , zatosetron )Verapamil Zinc NMDAR Tooltip N-Methyl-D-aspartate receptor
Transporter (blockers )
GlyT1 Tooltip Glycine transporter 1 GlyT2 Tooltip Glycine transporter 2
