415903-37-6 Usage
Description
Grapiprant, also known as CJ-023423, is a potent and selective antagonist of the E prostanoid 4 (EP4) receptor. It is a compound that plays a significant role in various biological processes, including bone formation and resorption, cancer, and atherosclerosis. Grapiprant is characterized by its high selectivity and potency, with Ki values of 13 and 20 nM for human and rat EP4 receptors, respectively.
Uses
Used in Pharmaceutical Industry:
Grapiprant is used as an antagonist for the EP4 receptor to inhibit PGE2-evoked elevation in intracellular cAMP in cells. This application is crucial in the development of treatments for various conditions, such as bone disorders, cancer, and atherosclerosis.
Used in Pain Management:
Grapiprant is used as an anti-inflammatory agent to reduce acute and chronic inflammatory pain in different mouse models. By blocking the EP4 receptor, it helps alleviate pain associated with inflammation and other related conditions.
Used in Cancer Research:
Grapiprant is used as a research tool to study the role of the EP4 receptor in cancer progression and metastasis. Its potent and selective antagonism of the EP4 receptor allows researchers to investigate the underlying mechanisms of cancer development and identify potential therapeutic targets.
Used in Atherosclerosis Research:
Grapiprant is used as a research compound to explore the involvement of the EP4 receptor in atherosclerosis. By understanding the role of this receptor in the disease process, researchers can develop novel strategies for the prevention and treatment of atherosclerosis.
Biological Functions
Grapiprant (CJ-023423) is an orally available, a potent and selective EP4 receptor antagonist that exhibits significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. Grapiprant is highly selective for the human EP4 receptor over other human prostanoid receptor subtypes. It also inhibits PGE2-evoked elevation in intracellular cAMP at the human and rat EP4 receptors with pA2 of 8.3 and 8.2 nM, respectively. In vivo, oral administration of grapiprant significantly reduces thermal hyperalgesia induced by intraplantar injection of PGE2 (ED50 = 12.8 mg/kg). It is also effective in models of acute and chronic inflammatory pain. Grapiprant significantly reduces mechanical hyperalgesia in the carrageenan model. Furthermore, it significantly reverses complete Freund′s adjuvant-induced chronic inflammatory pain response. It produces antihyperalgesic effects in animal models of inflammatory pain. Grapiprant is approved and widely used for treatment of osteoarthritis related pain in dogs. Grapiprant is classify as a non-cyclooxygenase inhibiting non-steroidal anti-inflammatory drug (NSAID).
in vitro
in vitro, cj-023,423 was able to inhibit [(3)h]pge(2) binding to both human and rat ep(4) receptors. cj-023,423 was found to be highly selective for the human ep(4) receptor over other human prostanoid receptor subtypes. cj-023,423 also inhibited pge(2)-evoked elevation in intracellular camp at the human and rat ep(4) receptors with pa(2) of 8.3 and 8.2 nm, respectively [1].
in vivo
in vivo, po administration of cj-023,423 could significantly reduce the thermal hyperalgesia that was induced by i.p. injection of pge(2). cj-023,423 was also effective in models of acute and chronic inflammatory pain. in addition, cj-023,423 was able to significantly reduce mechanical hyperalgesia in the carrageenan model. furthermore, cj-023,423 reversed complete freund's adjuvant-induced chronic inflammatory pain response significantly [1].
References
1) Nakao?et al.?(2007),?CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties;?J. Pharmacol. Exp. Ther.?332?686
2) Okumura?et al.?(2008),?Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis;?J. Pharm. Pharmacol.?60?7235
3) Chen?et al.?(2010),?A novel antagonist of the prostaglandin E2 EP4 receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models;?Br. J. Pharmacol.?160?292
4) Wang and DuBois (2016),?Wang and DuBois (2016), The Role of Prostaglandin E2 in Tumor-Associated Immunosuppression;?Trends Mol. Med.?22?1
5) NCT03696212 and NCT03658772
Check Digit Verification of cas no
The CAS Registry Mumber 415903-37-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,1,5,9,0 and 3 respectively; the second part has 2 digits, 3 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 415903-37:
(8*4)+(7*1)+(6*5)+(5*9)+(4*0)+(3*3)+(2*3)+(1*7)=136
136 % 10 = 6
So 415903-37-6 is a valid CAS Registry Number.
415903-37-6Relevant articles and documents
PROCESS FOR PREPARATION OF GRAPIPRANT
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, (2021/03/19)
The invention relates to process for the preparation of grapiprant and its intermediates thereof. The invention also relates to grapiprant having a purity 98% or more and compounds of Formula (A), (B), (C) and (D) in an amount of 0.5 or less, relative to grapiprant, by area percentage of HPLC. The invention also relates to an amorphous form of grapiprant and process for preparation thereof.
GRAPIPRANT UNIT DOSAGE FORMS
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Paragraph 00580; 00584, (2020/05/12)
The present invention provides grapiprant unit dosage forms, and methods of use thereof for treating a proliferative disorder.
CRYSTAL FORMS OF AN IMIDAZOLE DERIVATIVE
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Page/Page column 43, (2008/06/13)
The invention relates to the essentially pure Λ/-[({2-[4-(2-Ethyl-4,6-dimethyl-1 H- imidazo[4,5-c]pyridin-1 -yl)phenyl]ethyl}amino)carbonyl]-4- methylbenzenesulfonamide Polymorph Forms A and B and to processes for the preparation of, compositions containi
