Chemistry:Zevaquenabant
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Short description: Chemical compound
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| Other names | S-MRI-1867; INV-101; MRI-1867 |
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| Formula | C25H21ClF3N5O2S |
| Molar mass | 547.98 g·mol−1 |
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
- ↑ 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. PMID 31926199.
- ↑ Cinar, Resat; Iyer, Malliga R.; Liu, Ziyi; Cao, Zongxian; Jourdan, Tony; Erdelyi, Katalin; Godlewski, Grzegorz; Szanda, Gergő et al. (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. PMID 27525312. PMC 4979564. https://insight.jci.org/articles/view/87336.
- ↑ 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.
- ↑ 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. PMID 31454063.
- ↑ Cinar, Resat; Gochuico, Bernadette R.; Iyer, Malliga R.; Jourdan, Tony; Yokoyama, Tadafumi; Park, Joshua K.; Coffey, Nathan J.; Pri-Chen, Hadass et al. (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. PMID 28422760. PMC 5396529. https://insight.jci.org/articles/view/92281.
- ↑ Padilha, Elias C.; Yang, Mengbi; Shah, Pranav; Wang, Amy Q.; Duan, Jianmin; Park, Joshua K.; Zawatsky, Charles N.; Malicdan, May Christine V. et al. (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. PMID 37890204.
- ↑ Cinar, R; Park, JK; Zawatsky, CN; Coffey, NJ; Bodine, SP; Abdalla, J; Yokoyama, T; Jourdan, T et al. (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. PMID 34323400.
- ↑ 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. PMID 34650521.
- ↑ Roger, Célia; Buch, Chloé; Muller, Tania; Leemput, Julia; Demizieux, Laurent; Passilly-Degrace, Patricia; Cinar, Resat; Iyer, Malliga R. et al. (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. PMID 32680936.
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