LIT-001

LIT-001 is a small-molecule oxytocin receptor agonist that was first described in the literature in 2018.[1][2][3] It is similar in structure to TC OT 39, another oxytocin receptor agonist.[1][2] Compared to TC OT 39 and WAY-267464, LIT-001 has greater selectivity for the oxytocin receptor over the vasopressin 1A receptor (V1A receptor).[1][2] LIT-001 shows antagonism of the V1A receptor only at high concentrations.[1][2] LIT-001 additionally acts as an agonist of the vasopressin 2 receptor (V2 receptor) at similar concentrations as for the oxytocin receptor.[2] This is unlikely to influence the oxytocin receptor-related behavioral effects of LIT-001 (as V2 receptors are not expressed in the brain), but may influence fluid homeostasis analogously to vasopressin.[1][2] Given via peripheral administration, LIT-001 reduces social deficits in a mouse model of autism.[1][2][3] It was the first small-molecule oxytocin receptor agonist to be shown to be able to do this.[1][2] LIT-001 shows blood–brain barrier permeability and has a relatively long elimination half-life, giving it an advantageous drug profile relative to peptide oxytocin receptor agonists like oxytocin itself.[1][3][4] LIT-001 may have potential as a therapeutic agent in the treatment of social disorders in humans.[1][2][3]

LIT-001
Identifiers
  • (2S)-2-(dimethylcarbamothioyl)-N-[[2-methyl-4-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepine-5-carbonyl)phenyl]methyl]pyrrolidine-1-carboxamide
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC28H33N7O2S
Molar mass531.68 g·mol−1
3D model (JSmol)
  • CC1=C(C=CC(=C1)C(=O)N2CC3=C(NC4=CC=CC=C42)N(N=C3)C)CNC(=O)N5CCC[C@H]5C(=S)N(C)C
  • InChI=1S/C28H33N7O2S/c1-18-14-19(11-12-20(18)15-29-28(37)34-13-7-10-24(34)27(38)32(2)3)26(36)35-17-21-16-30-33(4)25(21)31-22-8-5-6-9-23(22)35/h5-6,8-9,11-12,14,16,24,31H,7,10,13,15,17H2,1-4H3,(H,29,37)/t24-/m0/s1
  • Key:AOPORIRPXVMWSL-DEOSSOPVSA-N

References
  1. Nashar PE, Whitfield AA, Mikusek J, Reekie TA (2022). "The Current Status of Drug Discovery for the Oxytocin Receptor". Methods Mol Biol. 2384: 153–174. doi:10.1007/978-1-0716-1759-5_10. PMID 34550574.
  2. Gulliver D, Werry E, Reekie TA, Katte TA, Jorgensen W, Kassiou M (January 2019). "Targeting the Oxytocin System: New Pharmacotherapeutic Approaches". Trends Pharmacol Sci. 40 (1): 22–37. doi:10.1016/j.tips.2018.11.001. PMID 30509888.
  3. Frantz MC, Pellissier LP, Pflimlin E, Loison S, Gandía J, Marsol C, Durroux T, Mouillac B, Becker JA, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M (October 2018). "LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism". J Med Chem. 61 (19): 8670–8692. doi:10.1021/acs.jmedchem.8b00697. PMID 30199637.
  4. Hilfiger L, Zhao Q, Kerspern D, Inquimbert P, Andry V, Goumon Y, Darbon P, Hibert M, Charlet A (February 2020). "A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain". Sci Rep. 10 (1): 3017. doi:10.1038/s41598-020-59929-w. PMC 7033278. PMID 32080303.


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