Grapiprant
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MedKoo CAT#: 522545

CAS#: 415903-37-6

Description: Grapiprant, also known as CJ-023,423, RQ-00000007 and AAT-007, is a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties. In vitro, CJ-023,423 inhibits [(3)H]PGE(2) binding to both human and rat EP(4) receptors with K(i) of 13 +/- 4 and 20 +/- 1 nM, respectively. CJ-023,423 is highly selective for the human EP(4) receptor over other human prostanoid receptor subtypes. It also inhibits PGE(2)-evoked elevation in intracellular cAMP at the human and rat EP(4) receptors with pA(2) of 8.3 +/- 0.03 and 8.2 +/- 0.2 nM, respectively. In vivo, oral administration of CJ-023,423 significantly reduces thermal hyperalgesia induced by intraplantar injection of PGE(2) (ED(50) = 12.8 mg/kg).

Chemical Structure

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Grapiprant
CAS# 415903-37-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522545
Name: Grapiprant
CAS#: 415903-37-6
Chemical Formula: C26H29N5O3S
Exact Mass: 491.20
Molecular Weight: 491.610
Elemental Analysis: C, 63.52; H, 5.95; N, 14.25; O, 9.76; S, 6.52

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1450 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3850 2 weeks
Bulk inquiry

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

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, 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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. 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

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.

Recalculate based on batch purity %
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.

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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.