From Wikipedia, the free encyclopedia
Chemical compound
Zevaquenabant
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Other names | S-MRI-1867; INV-101; MRI-1867 |
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(4S)-N-(1-Aminoethylidene)-5-(4-chlorophenyl)-4-phenyl-N′-[4-(trifluoromethyl)phenyl]sulfonyl-3,4-dihydropyrazole-2-carboximidamide
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PubChem
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Formula | C25H21ClF3N5O2S |
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Molar mass | 547.98 g·mol−1 |
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Zevaquenabant (S-MRI-1867, INV-101, or MRI-1867) is an investigational small-molecule drug, discovered by the
National Institutes of Health. Zevaquenabant was described as a third generation
cannabinoid receptor 1 (CB1R) antagonist due to its
peripheral selectivity and
polypharmacology.
[1] It acts as a peripherally selective
inverse agonist of the
cannabinoid receptor 1 and an
inducible nitric oxide synthase (iNOS) inhibitor.
[2]
[3] It has been studied in the experimental models of fibrotic disorders such as
liver fibrosis[1],
chronic kidney disease,
[4]
idiopathic pulmonary fibrosis,
[5]
Hermansky-Pudlak syndrome pulmonary fibrosis,
[6]
[7] skin fibrosis,
[8] and metabolic disorders such as
obesity[2] and
dyslipidemia.
[9]
References
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^ Cinar, R; Iyer, MR; Kunos, G (April 2020).
"The therapeutic potential of second and third generation CB(1)R antagonists". Pharmacology & Therapeutics. 208: 107477.
doi:
10.1016/j.pharmthera.2020.107477.
PMC
8605822.
PMID
31926199.
-
^ Cinar, Resat; Iyer, Malliga R.; Liu, Ziyi; Cao, Zongxian; Jourdan, Tony; Erdelyi, Katalin; Godlewski, Grzegorz; Szanda, Gergő; Liu, Jie; Park, Joshua K.; Mukhopadhyay, Bani; Rosenberg, Avi Z.; Lieow, Jeih-San; Lorenz, Robin G.; Pacher, Pal; Innis, Robert B.; Kunos, George (21 July 2016).
"Hybrid inhibitor of peripheral cannabinoid-1 receptors and inducible nitric oxide synthase mitigates liver fibrosis". JCI Insight. 1 (11).
doi:
10.1172/jci.insight.87336.
PMC
4979564.
PMID
27525312.
-
^ Iyer, Malliga R.; Cinar, Resat; Coffey, Nathan J.; Kunos, George (August 2018). "Synthesis of 13 C 6 -labeled, dual-target inhibitor of cannabinoid-1 receptor (CB 1 R) and inducible nitric oxide synthase (iNOS)". Journal of Labelled Compounds and Radiopharmaceuticals. 61 (10): 773–779.
doi:
10.1002/jlcr.3639.
PMID
29790591.
S2CID
46895177.
-
^ Udi, Shiran; Hinden, Liad; Ahmad, Majdoleen; Drori, Adi; Iyer, Malliga R.; Cinar, Resat; Herman-Edelstein, Michal; Tam, Joseph (January 2020).
"Dual inhibition of cannabinoid CB 1 receptor and inducible NOS attenuates obesity-induced chronic kidney disease". British Journal of Pharmacology. 177 (1): 110–127.
doi:
10.1111/bph.14849.
PMC
6976880.
PMID
31454063.
-
^ Cinar, Resat; Gochuico, Bernadette R.; Iyer, Malliga R.; Jourdan, Tony; Yokoyama, Tadafumi; Park, Joshua K.; Coffey, Nathan J.; Pri-Chen, Hadass; Szanda, Gergő; Liu, Ziyi; Mackie, Ken; Gahl, William A.; Kunos, George (20 April 2017).
"Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of idiopathic pulmonary fibrosis". JCI Insight. 2 (8).
doi:
10.1172/jci.insight.92281.
PMC
5396529.
PMID
28422760.
-
^ Padilha, Elias C.; Yang, Mengbi; Shah, Pranav; Wang, Amy Q.; Duan, Jianmin; Park, Joshua K.; Zawatsky, Charles N.; Malicdan, May Christine V.; Kunos, George; Iyer, Malliga R.; Gaucher, Geneviève; Ravenelle, François; Cinar, Resat; Xu, Xin (December 2023).
"In vitro and in vivo pharmacokinetic characterization, chiral conversion and PBPK scaling towards human PK simulation of S-MRI-1867, a drug candidate for Hermansky-Pudlak syndrome pulmonary fibrosis". Biomedicine & Pharmacotherapy. 168: 115178.
doi:
10.1016/j.biopha.2023.115178.
PMC
10715448.
PMID
37890204.
S2CID
264505730.
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^ Cinar, R; Park, JK; Zawatsky, CN; Coffey, NJ; Bodine, SP; Abdalla, J; Yokoyama, T; Jourdan, T; Jay, L; Zuo, MXG; O'Brien, KJ; Huang, J; Mackie, K; Alimardanov, A; Iyer, MR; Gahl, WA; Kunos, G; Gochuico, BR; Malicdan, MCV (July 2021).
"CB(1) R and iNOS are distinct players promoting pulmonary fibrosis in Hermansky-Pudlak syndrome". Clinical and Translational Medicine. 11 (7): e471.
doi:
10.1002/ctm2.471.
PMC
8255071.
PMID
34323400.
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^ Zawatsky, CN; Park, JK; Abdalla, J; Kunos, G; Iyer, MR; Cinar, R (2021).
"Peripheral Hybrid CB(1)R and iNOS Antagonist MRI-1867 Displays Anti-Fibrotic Efficacy in Bleomycin-Induced Skin Fibrosis". Frontiers in Endocrinology. 12: 744857.
doi:
10.3389/fendo.2021.744857.
PMC
8505776.
PMID
34650521.
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^ Roger, Célia; Buch, Chloé; Muller, Tania; Leemput, Julia; Demizieux, Laurent; Passilly-Degrace, Patricia; Cinar, Resat; Iyer, Malliga R.; Kunos, George; Vergès, Bruno; Degrace, Pascal; Jourdan, Tony (1 October 2020).
"Simultaneous Inhibition of Peripheral CB1R and iNOS Mitigates Obesity-Related Dyslipidemia Through Distinct Mechanisms". Diabetes. 69 (10): 2120–2132.
doi:
10.2337/db20-0078.
PMC
7506827.
PMID
32680936.