A potent, selective, brain permeable, orally available glycine transporter-1 (GlyT1) inhibitor with IC50 of 92 nM (rat GlyT1), 50-fold selectivity over GlyT2; shows minimal affinity for many other receptors except for μ-opioid receptors (IC50=1.83 uM); inhibits ex vivo [(3)H]-glycine uptake in mouse cortical homogenate, improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease. Schizophrenia Phase 1 Discontinued
MPDC is a potent and competitive inhibitor of the Na+-dependent high-affinity glutamate transporter in forebrain synaptosomes[1].
LY2365109 is a potent and selective GlyT1 inhibitors with IC50 value of 15.8 nM.target: GlyT1[1]IC 50: 15.8 nM [1]In vivo: The reference for LY2365109 is 0.3 or 30 mg/kg by PO. LY2365109 appeared slightly more potent than ALX5407 over the dose-range tested on CSF levels of glycine in the ratLY2365109 can act to potentiate NMDA function in the PFC but also mediate sustained inhibition of GlyT1 transporters in caudal areas of the brain.[1] LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109. [2]
Sarcosine is a glycine transporter type 1 (GlyT) inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site.
ALX-1393, a selective GlyT2 inhibitor, has an antinociceptive effect on thermal, mechanical, and chemical stimulations in a rat acute pain model[1].
ALX-5407 ((R)-NFPS) hydrochloride is a selective and orally active glycine transporter GlyT1 inhibitor with an IC50 value of 3 nM. ALX-5407 hydrochloride can be used the research of N-methyl-D-aspartate-receptor function and schizophrenia[1].
Org 25935 is a potent and selective glycine transporter 1 protein (GlyT1) inhibitor with an IC50 value of 100 nM. Org 25935 can decrease ethanol (EtOH) intake and EtOH preference in rats, whereas water intake is unaffected. Org 25935 can be used for researching alcohol dependence or abuse[1].
Opiranserin (VVZ-149) hydrochloride, a non-opioid and non-NSAID analgesic candidate, is a dual antagonist of glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with IC50s of 0.86 and 1.3 μM, respectively. Opiranserin hydrochloride shows antagonistic activity on rP2X3 (IC50=0.87 μM). Opiranserin hydrochloride is development as an injectable agent for the treatment of postoperative pain[1][2][3].
GlyT1 Inhibitor 1 is a potent and selective GlyT1 inhibitor with an IC50 of 38 nM for rGlyT1[1]. Antipsychotic activity[1].
Bitopertin is a potent, noncompetitive glycine reuptake inhibitor, inhibits glycine uptake at human GlyT1 with a concentration exhibiting IC50 of 25 nM.
N-Arachidonylglycine (NA-Gly), a carboxylic analog of the endocannabinoid anandamide (AEA), is a GPR18 agonist (EC50 = 44.5 nM). Unlike AEA, N-Arachidonylglycine has no activity at either CB1 or CB2 receptors. N-Arachidonylglycine inhibits GLYT2 (IC50 = 5.1 μM). N-Arachidonylglycine also is an effective activator of endometrial cell migration[1][2].
Bitopertin is a potent, noncompetitive glycine reuptake inhibitor, inhibits glycine uptake at human GlyT1 with a concentration exhibiting IC50 of 25 nM.
Org 25543 hydrochloride is a selective and irreversible GlyT2 inhibitor (IC50: 16 nM). Org 25543 hydrochloride has analgesia effect. Org 25543 hydrochloride ameliorates mechanical allodynia after partial sciatic nerve ligation injury in mice[1][2][3].
SSR504734 is an orally active, selective and reversible inhibitor of human, rat, and mouse GlyT1 (IC50=18, 15, and 38 nM, respectively). SSR504734 shows anti-schizophrenia, anti-anxiety and anti-depression activities[1].
A potent, selective, orally available GlyT1 inhibitor with Ki of 11.6 nM, without activity against GlyT2 (IC50>10 uM); demonstrates potent activity in elevating CSF levels of glycine in vivo (ED200, 3.5 mg/kg).
Stearoyl-L-carnitine chloride is an endogenous long-chain acylcarnitine. Stearoyl-L-carnitine chloride is a less potent inhibitor of GlyT2. Stearoyl-L-carnitine chloride inhibits glycine responses by 16.8% at concentrations up 3 μM[1][2].
Opiranserin (VVZ-149, VVZ-000149) is a potent, selective, mixed glycine GlyT2 transporter blocker (IC50= 0.86 uM), purine P2X3 receptor antagonist (IC50=0.87 uM) and serotonin 5-HT2A receptor antagonist (IC50=1.3 uM); demonstrates analgesic efficacy for postoperative pain. Pain Phase 2 Clinical
Sarcosine-d3 (N-Methylglycine-d3) is the deuterium labeled Sarcosine. Sarcosine (N-Methylglycine), an endogenous amino acid, is a competitive glycine transporter type I (GlyT1) inhibitor and N-methyl-D-aspartate (NMDA) receptor co-agonist. Sarcosine increases the glycine concentration, resulting in an indirect potentiation of the NMDA receptor. Sarcosine is commonly used for the research of schizophrenia[1][2].
Tilapertin is an oral inhibitor of glycine transporter type-1 (GlyT1).
NFPS is a selective, non-competitive glycine transporter-1 (GlyT1) inhibitor with IC50s of 2.8 nM and 9.8 nM for hGlyT1 and rGlyT1, respectively[1]. NFPS exerts neuroprotection via glyR alpha1 subunit in the rat model of transient focal cerebral ischaemia and reperfusion[2].
GlyT2-IN-1 is a glycine transporters GLYT2 inhibitor.Target: GLYT2The Glycine Transporter GlyT2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons. GlyT2-IN-1 is a novel agonist of the mechanotransduction channel Piezo1, eliciting Ca2+ flux in Piezo1- but not vector-transfected cells.