ALX-1393

Glycine reuptake inhibitor

ALX-1393^[1]
Names

IUPAC name (2S)-2-Amino-3-[(3-fluorophenyl)-(2-phenylmethoxyphenyl)methoxy]propanoic acid
Identifiers
CAS Number	949164-09-4
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL475562
ChemSpider	115042561
IUPHAR/BPS	4622
PubChem CID	16078939
InChI 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
SMILES C1=CC=C(C=C1)COC2=CC=CC=C2C(C3=CC(=CC=C3)F)OCC(C(=O)O)N
Properties
Chemical formula	C₂₃H₂₂FNO₄
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). Infobox references

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.

Glycine receptor modulators

Receptor
(ligands)

GlyRTooltip Glycine receptor	Agonists: β-Alanine β-ABA (BABA) β-AIBA Caesium D-Alanine D-Serine GABA Glycine Hypotaurine Ivermectin L-Alanine L-Proline L-Serine L-Threonine MDL-27531 Milacemide Picolinic acid Propofol Quisqualamine Sarcosine Taurine 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
NMDARTooltip N-Methyl-D-aspartate receptor	See here instead.

GlyRTooltip Glycine receptor

Agonists: β-Alanine
β-ABA (BABA)
β-AIBA
Caesium
D-Alanine
D-Serine
GABA
Glycine
Hypotaurine
Ivermectin
L-Alanine
L-Proline
L-Serine
L-Threonine
MDL-27531
Milacemide
Picolinic acid
Propofol
Quisqualamine
Sarcosine
Taurine

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

NMDARTooltip N-Methyl-D-aspartate receptor

See here instead.

Transporter
(blockers)

GlyT1Tooltip Glycine transporter 1	ACPPB ALX-5407 (NFPS) AMG-747 ASP2535 Bitopertin (RG1678/RO4917838) CP-802079 Ethanol (alcohol) Glycyldodecylamide GSK1018921 LY-2365109 ORG-24598 ORG-25935 (SCH-900435) Pesampator (BIIB-104, PF-04958242) PF-02545920 (Mardepodect) PF-03463275 Sarcosine SSR-103,800 SSR-504,734
GlyT2Tooltip Glycine transporter 2	ALX-1393 Amoxapine Ethanol (alcohol) NAGly Opiranserin (VVZ-149) ORG-25543 VVZ-368

See also: Receptor/signaling modulators; GABA receptor modulators; GABA_A receptor positive modulators; Ionotropic glutamate receptor modulators