Synonym
CJ-023423; CJ 023423; CJ023423; CAS#415903-37-6; RQ-00000007; RQ 00000007; RQ00000007; AAT-007; AAT007; AAT 007; Grapiprant
IUPAC/Chemical Name
N-((4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenethyl)carbamoyl)-4-methylbenzenesulfonamide
InChi Key
HZVLFTCYCLXTGV-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H29N5O3S/c1-5-24-29-25-19(4)28-18(3)16-23(25)31(24)21-10-8-20(9-11-21)14-15-27-26(32)30-35(33,34)22-12-6-17(2)7-13-22/h6-13,16H,5,14-15H2,1-4H3,(H2,27,30,32)
SMILES Code
O=C(NCCC1=CC=C(C=C1)N2C(CC)=NC3=C(N=C(C=C32)C)C)NS(C4=CC=C(C=C4)C)(=O)=O
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, not in water
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
More Info
CJ-023,423 is also effective in models of acute and chronic inflammatory pain. CJ-023,423 significantly reduces mechanical hyperalgesia in the carrageenan model. Furthermore, CJ-023,423 significantly reverses complete Freund's adjuvant-induced chronic inflammatory pain response. Taken together, the present data indicate that CJ-023,423, a highly potent and selective antagonist of both human and rat EP(4) receptors, produces antihyperalgesic effects in animal models of inflammatory pain. Thus, specific blockade of the EP(4) receptor signaling may represent a novel therapeutic approach for the treatment of inflammatory pain.
Biological target:
Grapiprant (CJ-023423) is a selective EP4 receptor antagonist whose physiological ligand is prostaglandin E2 (PGE2). Grapiprant displaces [3H]-PGE2 (1 nM) binding to dog recombinant EP4 receptor with IC50 value of 35 nM and Ki value of 24 nM.
In vitro activity:
PGE2 dose-dependently increased intracellular cAMP accumulation at human EP4 receptors expressed in HEK293 cells. Increasing concentrations of CJ-023,423 produced a rightward shift in the concentration-response curve for PGE2 without modulating the maximal cAMP production (Fig. 3A). The pA2 value was calculated as 8.3 ± 0.03 with a slope of 1.3 ± 0.1 (n = 3) by Schild plot analysis . These experiments were repeated using HEK293 cells transfected with cDNA encoding the rat EP4 receptor, resulting in a pA2 value of 8.2 ± 0.2 with a slope of 1.2 ± 0.1 (n = 4) (Fig. 3B). CJ-023,423 did not show any agonist activity at the human and rat recombinant EP4 receptors (data not shown). These data suggest that CJ-023,423 is a competitive antagonist at the human and rat EP4 receptors.
Reference: J Pharmacol Exp Ther. 2007 Aug;322(2):686-94. https://jpet.aspetjournals.org/content/322/2/686.long
In vivo activity:
This randomized, placebo-controlled masked study of a prostaglandin EP4 receptor antagonist for the control of pain and inflammation in dogs with OA (osteoarthritis) showed that grapiprant treatment resulted in a significant number of dogs with decreased PSS and PIS, as evaluated by the owner, and a decrease in the TOS, as evaluated by the veterinarian. In addition, grapiprant used for 28 days in this population of dogs was found to be safe. Adverse events were relatively mild and of short duration. No dog was withdrawn from the study, despite a higher frequency of transient vomiting in the grapiprant-treated dogs. These findings are important because grapiprant represents the first approach to daily PO treatment of pain and inflammation in dogs with OA with a mechanism of action targeted to binding and antagonizing a prostaglandin receptor (EP4) rather than inhibiting cyclooxygenase enzymes.
Reference: J Vet Intern Med. 2016 May-Jun; 30(3): 756–763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913586/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
61.02 |
| DMF |
20.0 |
40.68 |
| DMF:PBS (pH 7.2) (1:3) |
0.3 |
0.51 |
| Ethanol |
10.0 |
20.34 |
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
491.61
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:
2. Nakao K, Murase A, Ohshiro H, Okumura T, Taniguchi K, Murata Y, Masuda M, Kato T, Okumura Y, Takada J. CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties. J Pharmacol Exp Ther. 2007 Aug;322(2):686-94. doi: 10.1124/jpet.107.122010. Epub 2007 May 10. PMID: 17495127.1. Rausch-Derra L, Huebner M, Wofford J, Rhodes L. A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis. J Vet Intern Med. 2016 May;30(3):756-63. doi: 10.1111/jvim.13948. Epub 2016 Apr 13. PMID: 27075237; PMCID: PMC4913586.
3. Kirkby Shaw K, Rausch-Derra LC, Rhodes L. Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation. Vet Med Sci. 2015 Dec 21;2(1):3-9. doi: 10.1002/vms3.13. PMID: 29067176; PMCID: PMC5645826.
In vitro protocol:
1. Nakao K, Murase A, Ohshiro H, Okumura T, Taniguchi K, Murata Y, Masuda M, Kato T, Okumura Y, Takada J. CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties. J Pharmacol Exp Ther. 2007 Aug;322(2):686-94. doi: 10.1124/jpet.107.122010. Epub 2007 May 10. PMID: 17495127.
In vivo protocol:
1. Rausch-Derra L, Huebner M, Wofford J, Rhodes L. A Prospective, Randomized, Masked, Placebo-Controlled Multisite Clinical Study of Grapiprant, an EP4 Prostaglandin Receptor Antagonist (PRA), in Dogs with Osteoarthritis. J Vet Intern Med. 2016 May;30(3):756-63. doi: 10.1111/jvim.13948. Epub 2016 Apr 13. PMID: 27075237; PMCID: PMC4913586.
2. Kirkby Shaw K, Rausch-Derra LC, Rhodes L. Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain and inflammation. Vet Med Sci. 2015 Dec 21;2(1):3-9. doi: 10.1002/vms3.13. PMID: 29067176; PMCID: PMC5645826.
1: Vito VD, Saba A, Lee HK, Owen H, Poapolathep A, Giorgi M. Detection and
quantification of the selective EP4 receptor antagonist CJ-023423 (grapiprant) in
canine plasma by HPLC with spectrofluorimetric detection. J Pharm Biomed Anal.
2016 Jan 25;118:251-8. doi: 10.1016/j.jpba.2015.11.004. Epub 2015 Nov 7. PubMed
PMID: 26580822.
2: Okumura T, Murata Y, Taniguchi K, Murase A, Nii A. Effects of the selective
EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat
adjuvant-induced arthritis. J Pharm Pharmacol. 2008 Jun;60(6):723-30. doi:
10.1211/jpp.60.6.0007. PubMed PMID: 18498708.
3: Murase A, Nakao K, Takada J. Characterization of binding affinity of
CJ-023,423 for human prostanoid EP4 receptor. Pharmacology. 2008;82(1):10-4. doi:
10.1159/000125674. Epub 2008 Apr 11. PubMed PMID: 18408415.
4: Nakao K, Murase A, Ohshiro H, Okumura T, Taniguchi K, Murata Y, Masuda M, Kato
T, Okumura Y, Takada J. CJ-023,423, a novel, potent and selective prostaglandin
EP4 receptor antagonist with antihyperalgesic properties. J Pharmacol Exp Ther.
2007 Aug;322(2):686-94. Epub 2007 May 10. PubMed PMID: 17495127.
