Clinical data
Other namesS-MRI-1867; INV-101; MRI-1867
Legal status
Legal status
  • Investigational
  • (4S)-N-(1-Aminoethylidene)-5-(4-chlorophenyl)-4-phenyl-N-[4-(trifluoromethyl)phenyl]sulfonyl-3,4-dihydropyrazole-2-carboximidamide
CAS Number
PubChem CID
Chemical and physical data
Molar mass547.98 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]


  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.