LIT-001
目录号 : GC38922LIT-001 trifluoroacetate(LIT-001 TFA) is the first nonpeptide oxytocin receptor (OXTR) agonist that improves social interaction in a mouse model of autism.
Cas No.:2245072-21-1
Sample solution is provided at 25 µL, 10mM.
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LIT-001 trifluoroacetate(LIT-001 TFA) is the first nonpeptide oxytocin receptor (OXTR) agonist that improves social interaction in a mouse model of autism.
[1] Frantz MC, et al. J Med Chem. 2018 Oct 11;61(19):8670-8692.
Cas No. | 2245072-21-1 | SDF | |
Canonical SMILES | O=C(N1[C@H](C(N(C)C)=S)CCC1)NCC2=CC=C(C(N3C4=CC=CC=C4NC(N(C)N=C5)=C5C3)=O)C=C2C.O=C(O)C(F)(F)F | ||
分子式 | C30H34F3N7O4S | 分子量 | 645.7 |
溶解度 | DMSO: 250 mg/mL (387.18 mM) | 储存条件 | Store at -20°C |
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10 mM | 0.1549 mL | 0.7744 mL | 1.5487 mL |
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LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism
J Med Chem 2018 Oct 11;61(19):8670-8692.PMID:30199637DOI:10.1021/acs.jmedchem.8b00697.
Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism spectrum disorders (ASD), and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified, and none of them has been shown to be efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral ip administration.
[Oxytocin and its receptor: molecular and therapeutic approaches]
Biol Aujourdhui 2022;216(3-4):125-130.PMID:36744978DOI:10.1051/jbio/2022013.
It is known since the fifties that oxytocin is a neurohormone synthesized in the brain and released in blood circulation to trigger uterus contraction during delivery. It is also involved in milk ejection during breast-feeding. Over the past 25 years, many other central and peripheral functions have been discovered, in particular for attachment between child and parents as well as between individuals and interaction between a human being and its social group. Over this period, we have studied the functional supramolecular architecture of the hormone bound to its receptor. This information was used to design pharmacological probes and drug candidates. This led to the discovery of the first non-peptide oxytocin receptor full agonist. This molecule, LIT-001, restores social interaction in an animal model of autism and paves the way for a treatment of this neurodevelopmental disorder.
A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain
Sci Rep 2020 Feb 20;10(1):3017.PMID:32080303DOI:10.1038/s41598-020-59929-w.
Oxytocin possesses several physiological and social functions, among which an important analgesic effect. For this purpose, oxytocin binds mainly to its unique receptor, both in the central nervous system and in the peripheral nociceptive terminal axon in the skin. However, despite its interesting analgesic properties and its current use in clinics to facilitate labor, oxytocin is not used in pain treatment. Indeed, it is rapidly metabolized, with a half-life in the blood circulation estimated at five minutes and in cerebrospinal fluid around twenty minutes in humans and rats. Moreover, oxytocin itself suffers from several additional drawbacks: a lack of specificity, an extremely poor oral absorption and distribution, and finally, a lack of patentability. Recently, a first non-peptide full agonist of oxytocin receptor (LIT-001) of low molecular weight has been synthesized with reported beneficial effect for social interactions after peripheral administration. In the present study, we report that a single intraperitoneal administration of LIT-001 in a rat model induces a long-lasting reduction in inflammatory pain-induced hyperalgesia symptoms, paving the way to an original drug development strategy for pain treatment.
Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE
Neuropsychopharmacology 2022 Nov 11.PMID:36369481DOI:10.1038/s41386-022-01490-3.
Targeting the oxytocin (OXT) peptide system has emerged as a promising new approach for the treatment of alcohol use disorder (AUD). However, further advancements in this development depend on properly modeling various complex social aspects of AUD and its treatment. Here we examined behavioral and molecular underpinnings of OXT receptor (OXTR) agonism in prairie voles, a rodent species with demonstrated translational validity for neurobiological mechanisms regulating social affiliations. To further improve translational validity of these studies, we examined effects of intranasal (IN) OXT administration in male and female prairie voles socially housed in the presence of untreated cagemates. IN OXT selectively inhibited alcohol drinking in male, but not female, animals. Further, we confirmed that exogenously administered OXT penetrates the prairie vole brain and showed that Receptor for Advanced Glycation End-products assists this penetration after IN, but not intraperitoneal (IP), OXT administration. Finally, we demonstrated that IP administration of LIT-001, a small-molecule OXTR agonist, inhibits alcohol intake in male, but not female, prairie voles socially housed in the presence of untreated cagemates. Taken together, results of this study support the promise of selectively targeting OXTR for individualized treatment of AUD.