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]
^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.
Zevaquenabant (S-MRI-1867, INV-101, or MRI-1867) is an investigational small-molecule drug, discovered by the National Institutes of Health. Zevaquenabant...