GLYX13

• CAS: 1435786-04-1
• Catalog Number: ACM1435786041
• Category: Main Products
• Molecular Weight: 527.50
• Molecular Formula: C20H32F3N5O8
• Synonyms: Rapastinel Trifluoroacetate
• Appearance: White crystalline

Case Study

Molecular, cellular, and behavioral effects of GLYX-13

Liu, Rong-Jian, et al. Neuropsychopharmacology 42.6 (2017): 1231-1242.

GLYX-13 is a putative NMDA receptor modulator with glycine site partial agonist properties that produces rapid antidepressant effects. Researchers conducted studies examining the molecular, cellular, and behavioral effects of GLYX-13 to further characterize the mechanism of the drug's antidepressant effects. Results showed that a single dose of GLYX-13 rapidly activated the mTORC1 pathway in the prefrontal cortex (PFC), and that infusion of the selective mTORC1 inhibitor rapamycin into the medial PFC (mPFC) blocked the antidepressant behavioral effects of GLYX-13. The requirement for mTORC1 is similar to that of ketamine. Results also showed that GLYX-13 rapidly increased the number and function of spine synapses in the apical dendritic tufts of layer V pyramidal neurons in the mPFC. Notably, GLYX-13 significantly increased synaptic responses to hypocretin (a measure of thalamocortical synapses) compared to effects on 5-HT responses (a measure of 5-HT receptor-mediated cortical responses). Behavioral studies further showed that GLYX-13 did not affect 5-HT receptor-induced head twitch responses or impulsivity in the serial reaction time task (SRTT), whereas ketamine increased responses in both tests. In contrast, both GLYX-13 and ketamine increased attention in the SRTT task, which was associated with hypocretin-thalamocortical responses. Differences in 5-HT receptor synaptic and behavioral responses may be related to the lack of psychotomimetic side effects of GLYX-13 compared with ketamine, and modulation of hypocretin responses may contribute to the therapeutic effects of both rapid-acting antidepressants.
Data for signaling proteins were analyzed using one-way ANOVA. Data for behavioral tests of antidepressant-like activity and locomotor activity were analyzed using Kruskal-Wallis tests. Treatment groups were compared to the veh/veh control group using post hoc Dunn's test. In cases of unequal or small group sizes (n = 4 or 5), effect sizes were also calculated and reported as Cohen's d/Hedge's g values for standardized mean differences. Treatment effects in the SRTT were assessed using repeated measures two-way ANOVA (treatment × trial type), and post hoc pairwise comparisons of ketamine and GLYX-13 treatments relative to the respective control groups were performed using Student's t test with Bonferroni correction. Results are presented as mean ± SEM. Analyses were performed using SPSS or GraphPad Prism 6 software.

GLYX-13 has the potential to treat autism

Moskal, Joseph R., et al. Neuroscience & Biobehavioral Reviews 35.9 (2011): 1982-1988.

Deficits in social behavior, rough-and-tumble play, and speech abnormalities are core features of autism that can be modeled in laboratory mice. A review found that 99 genes are dysregulated in human autism. Bioinformatic analysis of these 99 genes identified the NMDA receptor complex as an important interaction hub based on protein-protein interactions. The NMDA receptor glycine site partial agonist d-cycloserine has been shown to treat core symptoms of social withdrawal in children with autism. Selectively bred mice can be used to model some of the core symptoms of autism. Compared to non-selectively bred random line animals, low-line animals spent less time in social contact with conspecifics, showed lower rates of play-induced prosocial USVs, and showed an increased proportion of non-frequency modulated (i.e., monotonic) ultrasonic vocalizations in low-line animals. Gene expression patterns in low-line animals showed significant enrichment for autism-associated genes, and the NMDA receptor family was identified as an important hub. Treatment of low-line animals with the NMDAR glycine site partial agonist GLYX-13 rescued deficits in play-induced prosocial 50-kHz and reduced monotonous USVs. Thus, NMDA receptors have been shown to play a functional role in autism, and GLYX-13 shows promise as a treatment for autism.
Multiple data suggest that GLYX-13 is a partial agonist at the NMDAR glycine site. First, GLYX-13 was derived from one of the hypervariable regions of the light chain of a monoclonal antibody that was shown to act as a partial agonist at the NMDA receptor glycine site. GLYX-13 was identified by measuring the binding of H-MK801 to rat hippocampal membrane preparations in the presence of saturating concentrations of the NMDAR glycine site-specific competitive antagonist 7-chlorokynurenine. GLYX-13 was found to be able to overcome this blockade in a concentration-dependent manner and to be incompatible with d-cycloserine. Secondly, the partial agonist properties of GLYX-13 were examined by performing a DC analysis using NMDARs expressed in frog oocytes. It can be seen that GLYX-13 activates these currents in the absence of glycine but in the presence of the co-agonist glutamate, inhibits the currents in the presence of an optimal concentration of glycine, and competes with 7-chloro-kynuric acid in a dose-dependent manner. This is exactly as expected for a glycine site-specific partial agonist. Thirdly, GLYX-13 showed similar behavior using rat hippocampal slices and measuring the enhancement of NMDAR currents and long-term potentiation. Fourthly, behavioral studies showed that low concentrations of GLYX-13 could enhance learning in various hippocampal-dependent learning tasks and inhibit neuropathic pain. Fifthly, using the cell patch clamp technique to measure NMDAR currents in hippocampal slices and identify partial agonists following the Stephenson protocol, it was found that GLYX-13 again acted as a partial agonist by facilitating currents in the presence of low concentrations of d-serine.

Custom Q&A

What is the molecular formula of GLYX13?

The molecular formula of GLYX13 is C18H31N5O6.

What are the synonyms of GLYX13?

The synonyms of GLYX13 are Rapastinel, 117928-94-6, TPPT-amide, and GLYX 13.

What is the molecular weight of GLYX13?

The molecular weight of GLYX13 is 413.5 g/mol.

When was GLYX13 created?

GLYX13 was created on February 9, 2007.

When was GLYX13 last modified?

GLYX13 was last modified on October 21, 2023.

What is the structure of GLYX13?

The structure of GLYX13 can be viewed at the provided link: https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi?cid=14539800&t=l

What is the IUPAC name of GLYX13?

The IUPAC name of GLYX13 is "(2S)-1-[(2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]-N-[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]pyrrolidine-2-carboxamide".

What is the InChI key of GLYX13?

The InChI key of GLYX13 is "GIBQQARAXHVEGD-BSOLPCOYSA-N".

What is the CAS number of GLYX13?

The CAS number of GLYX13 is 117928-94-6.

What is the XLogP3-AA value of GLYX13?

The XLogP3-AA value of GLYX13 is -2.8.