Synonym
ER819762; ER 819762; ER-819762
IUPAC/Chemical Name
(5S)-1'-[(3,5-dimethylphenyl)methyl]-2-ethyl-6,8-dimethoxy-5-methylspiro[5,10-dihydroimidazo[1,5-b][2]benzazepine-3,4'-piperidine]-1-one
InChi Key
JHKJPRFJRFDWPD-QFIPXVFZSA-N
InChi Code
InChI=1S/C30H39N3O3/c1-7-32-29(34)26-9-8-24-17-25(35-5)18-27(36-6)28(24)22(4)33(26)30(32)10-12-31(13-11-30)19-23-15-20(2)14-21(3)16-23/h9,14-18,22H,7-8,10-13,19H2,1-6H3/t22-/m0/s1
SMILES Code
O=C1N(CC)C2(CCN(CC3=CC(C)=CC(C)=C3)CC2)N4C1=CCC5=CC(OC)=CC(OC)=C5[C@@H]4C
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:
Potent EP4 receptor antagonist.
In vitro activity:
ER-819762 also suppressed human EP4 receptor-mediated cell signalling as measured in a cAMP-dependent reporter assay (IC50 value of 59 ± 6 nmol·L−1) (Fig. 1B). In a larger cell signalling panel of 107 GPCRs, ER-819762 (1 µmol·L−1) was highly selective for EP4 receptors, exhibiting no agonism or antagonism for any other receptor, including the related PGE2 EP1, EP2 and EP3 receptors (Table 1).
Reference: Br J Pharmacol. 2010 May; 160(2): 292–310. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874852/
In vivo activity:
This study first tested the effect of ER-819762 in the murine CIA model, an animal model widely used for assessing therapeutic agents for treatment of RA. When given orally prior to the onset of disease, ER-819762 dose-dependently suppressed the clinical signs of arthritis and delayed disease onset (Fig. 6A). ER-819762 also significantly suppressed disease progression when it was administered subsequent to the onset of disease (Fig. 6B). Furthermore, ER-819762 retarded bone erosion in the CIA model, as demonstrated by radiological evaluation (Fig. 6C).
Reference: Br J Pharmacol. 2010 May; 160(2): 292–310. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874852/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
1.0 |
2.00 |
| Ethanol |
2.5 |
5.00 |
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
489.66
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. Chen Q, Muramoto K, Masaaki N, Ding Y, Yang H, Mackey M, Li W, Inoue Y, Ackermann K, Shirota H, Matsumoto I, Spyvee M, Schiller S, Sumida T, Gusovsky F, Lamphier M. A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310. doi: 10.1111/j.1476-5381.2010.00647.x. PMID: 20423341; PMCID: PMC2874852.
In vitro protocol:
1. Chen Q, Muramoto K, Masaaki N, Ding Y, Yang H, Mackey M, Li W, Inoue Y, Ackermann K, Shirota H, Matsumoto I, Spyvee M, Schiller S, Sumida T, Gusovsky F, Lamphier M. A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310. doi: 10.1111/j.1476-5381.2010.00647.x. PMID: 20423341; PMCID: PMC2874852.
In vivo protocol:
1. Chen Q, Muramoto K, Masaaki N, Ding Y, Yang H, Mackey M, Li W, Inoue Y, Ackermann K, Shirota H, Matsumoto I, Spyvee M, Schiller S, Sumida T, Gusovsky F, Lamphier M. A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310. doi: 10.1111/j.1476-5381.2010.00647.x. PMID: 20423341; PMCID: PMC2874852.
1: Jones VC, Birrell MA, Maher SA, Griffiths M, Grace M, O'Donnell VB, Clark SR, Belvisi MG. Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2. Br J Pharmacol. 2016 Mar;173(6):992-1004. doi: 10.1111/bph.13400. PubMed PMID: 26639895; PubMed Central PMCID: PMC4831025.
2: Chen Q, Muramoto K, Masaaki N, Ding Y, Yang H, Mackey M, Li W, Inoue Y, Ackermann K, Shirota H, Matsumoto I, Spyvee M, Schiller S, Sumida T, Gusovsky F, Lamphier M. A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310. doi: 10.1111/j.1476-5381.2010.00647.x. PubMed PMID: 20423341; PubMed Central PMCID: PMC2874852.
