Monlunabant

Monlunabant
Clinical data
Other names	INV-202, MRI-1891
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name N-[(E)-N′-[(Z)-C-[(4S)-5-(4-Chlorophenyl)-4-phenyl-3,4-dihydropyrazol-2-yl]-N-[4-(trifluoromethyl)phenyl]sulfonylcarbonimidoyl]carbamimidoyl]acetamide;
CAS Number	2712480-46-9;
PubChem CID	164888943;
ChemSpider	128942559;
UNII	4G8X27X87A;
Chemical and physical data
Formula	C26H22ClF3N6O3S
Molar mass	591.01 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(=O)N/C(=N/C(=N/S(=O)(=O)C1=CC=C(C=C1)C(F)(F)F)/N2C[C@@H](C(=N2)C3=CC=C(C=C3)Cl)C4=CC=CC=C4)/N;
	InChI InChI=1S/C26H22ClF3N6O3S/c1-16(37)32-24(31)33-25(35-40(38,39)21-13-9-19(10-14-21)26(28,29)30)36-15-22(17-5-3-2-4-6-17)23(34-36)18-7-11-20(27)12-8-18/h2-14,22H,15H2,1H3,(H3,31,32,33,35,37)/t22-/m1/s1; Key:GYJPQNPVIJXXTA-JOCHJYFZSA-N;

Monlunabant (INV-202, MRI-1891, or S-MRI-1891) is a peripherally selective cannabinoid receptor 1 inverse agonist, discovered as a β-arrestin-2-biased cannabinoid receptor 1 antagonist by the National Institutes of Health.^[1] It was developed as a weight loss drug by Inversago Pharma.^[2]^[3]^[4]

Novo Nordisk’s obesity drug monlunabant showed only modest weight loss in a Phase 2a trial.^[5] The drug was associated with higher rates of mild to moderate neuropsychiatric side effects like anxiety and sleep disturbances.^[6] While suicidal ideations were not reported, the results highlight challenges for Novo in developing new obesity treatments beyond Wegovy.

References

^ Liu, Ziyi; Iyer, Malliga R.; Godlewski, Grzegorz; Jourdan, Tony; Liu, Jie; Coffey, Nathan J.; Zawatsky, Charles N.; Puhl, Henry L.; Wess, Jürgen; Meister, Jaroslawna; Liow, Jeih-San; Innis, Robert B.; Hassan, Sergio A.; Lee, Yong Sok; Kunos, George; Cinar, Resat (11 June 2021). "Functional Selectivity of a Biased Cannabinoid-1 Receptor (CB 1 R) Antagonist". ACS Pharmacology & Translational Science. 4 (3): 1175–1187. doi:10.1021/acsptsci.1c00048. PMC 8204328. PMID 34151207.</
^ Crater, Glenn D.; Ravenelle, Francois; Lalonde, Karine; DespréS, Jean-Pierre (20 June 2023). "431-P: Effects of CB1 Antagonist INV-202 in Patients with Metabolic Syndrome—A Randomized, Placebo-Controlled, Double-Blind Phase 1B Study". Diabetes. 72 (Supplement_1). doi:10.2337/db23-431-P. S2CID 259384475.
^ Morris, C.R.; Chandrasekaran, R.; Butzirius, I.; Daphtary, N.; Aliyeva, M.; Bates, J.H.T.; Anathy, V.; Crater, G.D.; Gaucher, G.; Dixon, A.E. (May 2023). "Cannabinoid Receptor 1 Inverse Agonist, INV-202, Induces Weight Loss and Reduces Airway Hyperreactivity in a Mouse Model of Obese Asthma". B15. Asthma: Hot off the Press from the Bench to the Clinic. pp. A2759. doi:10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A2759. S2CID 258446002.
^ Crater, Glenn D.; Lalonde, Karine; Ravenelle, François; Harvey, Michael; Després, Jean-Pierre (8 November 2023). "Effects of CB1R inverse agonist, INV -202, in patients with features of metabolic syndrome. A randomized, placebo-controlled, double-blind phase 1b study". Diabetes, Obesity and Metabolism. 26 (2): 642–649. doi:10.1111/dom.15353. PMID 37941317.
^ Chen, Elaine (2024-09-20). "Novo's new obesity drug shows modest results, raises concerns of psychiatric side effects". STAT. Retrieved 2024-09-21.
^ "News Details". Novo Nordisk. Retrieved 2024-09-21.

[1] Liu, Ziyi; Iyer, Malliga R.; Godlewski, Grzegorz; Jourdan, Tony; Liu, Jie; Coffey, Nathan J.; Zawatsky, Charles N.; Puhl, Henry L.; Wess, Jürgen; Meister, Jaroslawna; Liow, Jeih-San; Innis, Robert B.; Hassan, Sergio A.; Lee, Yong Sok; Kunos, George; Cinar, Resat (11 June 2021). "Functional Selectivity of a Biased Cannabinoid-1 Receptor (CB 1 R) Antagonist". ACS Pharmacology & Translational Science. 4 (3): 1175–1187. doi:10.1021/acsptsci.1c00048. PMC 8204328. PMID 34151207.</

[2] Crater, Glenn D.; Ravenelle, Francois; Lalonde, Karine; DespréS, Jean-Pierre (20 June 2023). "431-P: Effects of CB1 Antagonist INV-202 in Patients with Metabolic Syndrome—A Randomized, Placebo-Controlled, Double-Blind Phase 1B Study". Diabetes. 72 (Supplement_1). doi:10.2337/db23-431-P. S2CID 259384475.

[3] Morris, C.R.; Chandrasekaran, R.; Butzirius, I.; Daphtary, N.; Aliyeva, M.; Bates, J.H.T.; Anathy, V.; Crater, G.D.; Gaucher, G.; Dixon, A.E. (May 2023). "Cannabinoid Receptor 1 Inverse Agonist, INV-202, Induces Weight Loss and Reduces Airway Hyperreactivity in a Mouse Model of Obese Asthma". B15. Asthma: Hot off the Press from the Bench to the Clinic. pp. A2759. doi:10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A2759. S2CID 258446002.

[4] Crater, Glenn D.; Lalonde, Karine; Ravenelle, François; Harvey, Michael; Després, Jean-Pierre (8 November 2023). "Effects of CB1R inverse agonist, INV -202, in patients with features of metabolic syndrome. A randomized, placebo-controlled, double-blind phase 1b study". Diabetes, Obesity and Metabolism. 26 (2): 642–649. doi:10.1111/dom.15353. PMID 37941317.

[5] Chen, Elaine (2024-09-20). "Novo's new obesity drug shows modest results, raises concerns of psychiatric side effects". STAT. Retrieved 2024-09-21.

[6] "News Details". Novo Nordisk. Retrieved 2024-09-21.

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