From Wikipedia, the free encyclopedia
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
395.430 g·mol−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
ALX-1393 works by inhibiting the action of
GLYT2 .
[2] This causes elevated levels of glycine, an inhibitory neurotransmitter.
Potential uses
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
^
"(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