Synonym
SC-51089 hydrochloride; SC-51089 HCl; SC-51089; SC 51089; SC51089; CID132748; CID-132748; CID 132748.
IUPAC/Chemical Name
8-chloro-N'-(3-(pyridin-4-yl)propanoyl)dibenzo[b,f][1,4]oxazepine-10(11H)-carbohydrazide hydrochloride
InChi Key
ORMHJTXDPDGKIS-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H19ClN4O3.ClH/c23-17-6-7-20-18(13-17)27(14-16-3-1-2-4-19(16)30-20)22(29)26-25-21(28)8-5-15-9-11-24-12-10-15;/h1-4,6-7,9-13H,5,8,14H2,(H,25,28)(H,26,29);1H
SMILES Code
ClC1=CC2=C(OC3=CC=CC=C3CN2C(NNC(CCC4=CC=NC=C4)=O)=O)C=C1.Cl
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, DMF, and ethanol
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:
SC-51089 is an antagonist of PGE2 receptor subtype EP1 (Ki = 1.332 µM). It is selective for EP1 over EP2, EP3, and EP4 (Kis = >100, 17.5, and >100 µM, respectively), as well as the PGD2 receptor DP, PGF2α receptor FP, PGI2 receptor IP, and thromboxane A2 receptor TP (Kis = >100, 61.13, >100, and 11.18 µM, respectively).
In vitro activity:
In human neuroblastoma cell line (MC65), SC-51089 reduced Aβ neurotoxicity ~50 % without altering high molecular weight Aβ immunoreactive species formation. SC-51089 largely protected the murine primary cortical neuron cultures from synthetic Aβ(1-42) neurotoxicity.
Reference: J Neuroimmune Pharmacol. 2013 Mar;8(1):87-93. https://pubmed.ncbi.nlm.nih.gov/22718277/
In vivo activity:
In a mouse model of Huntington’s disease, administration of SC-51089 significantly improved motor coordination, balance, and long-term memory deficits in R6/1 mice. This treatment positively influenced the expression of synaptic markers, reduced the number of huntingtin nuclear inclusions in the striatum and hippocampus of 18-week-old R6/1 mice, and restored hippocampal long-term potentiation via EP1 receptor antagonism.
Reference: Mol Neurobiol. 2014 Apr;49(2):784-95. https://pubmed.ncbi.nlm.nih.gov/24198227/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
65.31 |
| DMSO |
20.0 |
43.54 |
| Ethanol |
30.0 |
65.31 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
459.33
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. Niu JC, Ma N, Liu W, Wang PJ. EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth. Bosn J Basic Med Sci. 2019 Aug 20;19(3):265-273. doi: 10.17305/bjbms.2019.4177. PMID: 30995899; PMCID: PMC6716101.
2. Li X, Rose SE, Montine KS, Keene CD, Montine TJ. Antagonism of neuronal prostaglandin E(2) receptor subtype 1 mitigates amyloid β neurotoxicity in vitro. J Neuroimmune Pharmacol. 2013 Mar;8(1):87-93. doi: 10.1007/s11481-012-9380-1. Epub 2012 Jun 21. PMID: 22718277; PMCID: PMC3700810.
3. Frankowski JC, DeMars KM, Ahmad AS, Hawkins KE, Yang C, Leclerc JL, Doré S, Candelario-Jalil E. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke. Sci Rep. 2015 Dec 9;5:17956. doi: 10.1038/srep17956. PMID: 26648273; PMCID: PMC4673693.
4. Anglada-Huguet M, Xifró X, Giralt A, Zamora-Moratalla A, Martín ED, Alberch J. Prostaglandin E2 EP1 receptor antagonist improves motor deficits and rescues memory decline in R6/1 mouse model of Huntington's disease. Mol Neurobiol. 2014 Apr;49(2):784-95. doi: 10.1007/s12035-013-8556-x. Epub 2013 Nov 7. PMID: 24198227.
In vitro protocol:
1. Niu JC, Ma N, Liu W, Wang PJ. EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth. Bosn J Basic Med Sci. 2019 Aug 20;19(3):265-273. doi: 10.17305/bjbms.2019.4177. PMID: 30995899; PMCID: PMC6716101.
2. Li X, Rose SE, Montine KS, Keene CD, Montine TJ. Antagonism of neuronal prostaglandin E(2) receptor subtype 1 mitigates amyloid β neurotoxicity in vitro. J Neuroimmune Pharmacol. 2013 Mar;8(1):87-93. doi: 10.1007/s11481-012-9380-1. Epub 2012 Jun 21. PMID: 22718277; PMCID: PMC3700810.
In vivo protocol:
1. Frankowski JC, DeMars KM, Ahmad AS, Hawkins KE, Yang C, Leclerc JL, Doré S, Candelario-Jalil E. Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke. Sci Rep. 2015 Dec 9;5:17956. doi: 10.1038/srep17956. PMID: 26648273; PMCID: PMC4673693.
2. Anglada-Huguet M, Xifró X, Giralt A, Zamora-Moratalla A, Martín ED, Alberch J. Prostaglandin E2 EP1 receptor antagonist improves motor deficits and rescues memory decline in R6/1 mouse model of Huntington's disease. Mol Neurobiol. 2014 Apr;49(2):784-95. doi: 10.1007/s12035-013-8556-x. Epub 2013 Nov 7. PMID: 24198227.
1: Hallinan EA, Hagen TJ, Tsymbalov S, Stapelfeld A, Savage MA. 2,4-Disubstituted oxazoles and thiazoles as latent pharmacophores for diacylhydrazine of SC-51089, a potent PGE2 antagonist. Bioorg Med Chem. 2001 Jan;9(1):1-6. PubMed PMID: 11197330.
2: Hallinan EA, Hagen TJ, Tsymbalov S, Husa RK, Lee AC, Stapelfeld A, Savage MA. Aminoacetyl moiety as a potential surrogate for diacylhydrazine group of SC-51089, a potent PGE2 antagonist, and its analogs. J Med Chem. 1996 Jan 19;39(2):609-13. PubMed PMID: 8558534.
3: Lee K, Vandenberghe Y, Herin M, Cavalier R, Beck D, Li A, Verbeke N, Lesne M, Roba J. Comparative metabolism of SC-42867 and SC-51089, two PGE2 antagonists, in rat and human hepatocyte cultures. Xenobiotica. 1994 Jan;24(1):25-36. PubMed PMID: 8165819.
