WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 532059
CAS#: 162042-44-6
Description: L-371,257 is a potent, high affinity human oxytocin (OT) receptor antagonist (Ki = 4.6 nM) that displays > 800-fold selectivity over human arginine vasopressin receptors V1a and V2. L-371,257 antagonizes oxytocin-induced contractions in isolated rat uterine tissue (pA2 = 8.44) and in anesthetised rats following intravenous and intraduodenal administration.
MedKoo Cat#: 532059
Name: L-371,257
CAS#: 162042-44-6
Chemical Formula: C28H33N3O6
Exact Mass: 507.2369
Molecular Weight: 507.587
Elemental Analysis: C, 66.26; H, 6.55; N, 8.28; O, 18.91
Synonym: L-371,257; L 371,257; L371,257; L-371257; L 371257; L371257;
IUPAC/Chemical Name: 1-[1-[4-(1-acetylpiperidin-4-yl)oxy-2-methoxybenzoyl]piperidin-4-yl]-4H-3,1-benzoxazin-2-one
InChi Key: WDERJSQJYIJOPD-UHFFFAOYSA-N
InChi Code: InChI=1S/C28H33N3O6/c1-19(32)29-15-11-22(12-16-29)37-23-7-8-24(26(17-23)35-2)27(33)30-13-9-21(10-14-30)31-25-6-4-3-5-20(25)18-36-28(31)34/h3-8,17,21-22H,9-16,18H2,1-2H3
SMILES Code: O=C1N(C2CCN(C(C3=CC=C(OC4CCN(C(C)=O)CC4)C=C3OC)=O)CC2)C5=CC=CC=C5CO1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | L-371,257 is an orally bioavailable, non-blood-brain barrier penetrant, selective and competitive antagonist of Oxytocin Receptor (pA2=8.4) with high affinity at both the oxytocin receptor (Ki=19 nM) and vasopressin V1a receptor (Ki=3.7 nM). |
| In vitro activity: | Slower growth rates and lower levels of phosphorylated ERK1/2 were observed in OXTR-knockdown cells and in U-87MG cells treated with an OXTR antagonist (L-371,257). Reference: Endocr Regul. 2020 Jul 1;54(3):172-182. https://pubmed.ncbi.nlm.nih.gov/32857718/ |
| In vivo activity: | By immunostaining tissues from OXTR-YFP knock-in mice, this study found that OXTR is expressed in a subset of Glial-like (Type I) taste cells, and also in cells on the periphery of taste buds. Using Ca2+ imaging, this study observed that physiologically appropriate concentrations of OXT (oxytocin) evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM). OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Reference: PLoS One. 2010 Aug 5;5(8):e11980. https://pubmed.ncbi.nlm.nih.gov/20700536/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.44 | 10.71 |
The following data is based on the product molecular weight 507.587 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Alanazi MM, Havranek T, Bakos J, Cubeddu LX, Castejon AM. Cell proliferation and anti-oxidant effects of oxytocin and oxytocin receptors: role of extracellular signal-regulating kinase in astrocyte-like cells. Endocr Regul. 2020 Jul 1;54(3):172-182. doi: 10.2478/enr-2020-0020. PMID: 32857718. 2. Sun LH, Tzeng WY, Liao YH, Deng WT, Cherng CG, Yu L. Relevance of number and physiological status of conspecifics in preventing stress-induced decreases in newly proliferated cells and neuroblasts. Psychopharmacology (Berl). 2019 Nov;236(11):3329-3339. doi: 10.1007/s00213-019-05290-4. Epub 2019 Jun 14. PMID: 31201477. 3. Sinclair MS, Perea-Martinez I, Dvoryanchikov G, Yoshida M, Nishimori K, Roper SD, Chaudhari N. Oxytocin signaling in mouse taste buds. PLoS One. 2010 Aug 5;5(8):e11980. doi: 10.1371/journal.pone.0011980. PMID: 20700536; PMCID: PMC2916830. 4. Ring RH, Malberg JE, Potestio L, Ping J, Boikess S, Luo B, Schechter LE, Rizzo S, Rahman Z, Rosenzweig-Lipson S. Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications. Psychopharmacology (Berl). 2006 Apr;185(2):218-25. doi: 10.1007/s00213-005-0293-z. Epub 2006 Jan 18. PMID: 16418825. |
| In vitro protocol: | 1. Alanazi MM, Havranek T, Bakos J, Cubeddu LX, Castejon AM. Cell proliferation and anti-oxidant effects of oxytocin and oxytocin receptors: role of extracellular signal-regulating kinase in astrocyte-like cells. Endocr Regul. 2020 Jul 1;54(3):172-182. doi: 10.2478/enr-2020-0020. PMID: 32857718. 2. Sun LH, Tzeng WY, Liao YH, Deng WT, Cherng CG, Yu L. Relevance of number and physiological status of conspecifics in preventing stress-induced decreases in newly proliferated cells and neuroblasts. Psychopharmacology (Berl). 2019 Nov;236(11):3329-3339. doi: 10.1007/s00213-019-05290-4. Epub 2019 Jun 14. PMID: 31201477. |
| In vivo protocol: | 1. Sinclair MS, Perea-Martinez I, Dvoryanchikov G, Yoshida M, Nishimori K, Roper SD, Chaudhari N. Oxytocin signaling in mouse taste buds. PLoS One. 2010 Aug 5;5(8):e11980. doi: 10.1371/journal.pone.0011980. PMID: 20700536; PMCID: PMC2916830. 2. Ring RH, Malberg JE, Potestio L, Ping J, Boikess S, Luo B, Schechter LE, Rizzo S, Rahman Z, Rosenzweig-Lipson S. Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications. Psychopharmacology (Berl). 2006 Apr;185(2):218-25. doi: 10.1007/s00213-005-0293-z. Epub 2006 Jan 18. PMID: 16418825. |
1: Williams PD, Bock MG, Evans BE, Freidinger RM, Gallicchio SN, Guidotti MT, Jacobson MA, Kuo MS, Levy MR, Lis EV, Michelson SR, Pawluczyk JM, Perlow DS, Pettibone DJ, Quigley AG, Reiss DR, Salvatore C, Stauffer KJ, Woyden CJ. Nonpeptide oxytocin antagonists: analogs of L-371,257 with improved potency. Bioorg Med Chem Lett. 1999 May 3;9(9):1311-6. PubMed PMID: 10340620.
2: Kuo MS, Bock MG, Freidinger RM, Guidotti MT, Lis EV, Pawluczyk JM, Perlow DS, Pettibone DJ, Quigley AG, Reiss DR, Williams PD, Woyden CJ. Nonpeptide oxytocin antagonists: potent, orally bioavailable analogs of L-371,257 containing a 1-R-(pyridyl)ethyl ether terminus. Bioorg Med Chem Lett. 1998 Nov 3;8(21):3081-6. PubMed PMID: 9873680.
3: Williams PD, Clineschmidt BV, Erb JM, Freidinger RM, Guidotti MT, Lis EV, Pawluczyk JM, Pettibone DJ, Reiss DR, Veber DF, et al. 1-(1-[4-[(N-acetyl-4-piperidinyl)oxy]-2-methoxybenzoyl]piperidin-4- yl)-4H-3,1-benzoxazin-2(1H)-one (L-371,257): a new, orally bioavailable, non-peptide oxytocin antagonist. J Med Chem. 1995 Nov 10;38(23):4634-6. PubMed PMID: 7473590.
