| Hazard Information | Back Directory | [Uses]
IDO2-IN-1 is an orally active and potent Indoleamine 2,3-dioxygenase 2 (IDO2) inhibitor with an IC50 value of 112 nM. IDO2-IN-1 can be used for inflammatory autoimmunity research[1]. | [in vivo]
The Adjuvant arthritis (AA) model and Collagen-induced arthritis (CIA) model have similar pathogenesis and pathological characteristics to human rheumatoid arthritis (RA).
IDO2-IN-1 (compound 22) (100 mg/kg; p.o.; once dose) exhibits excellent anti-inflammatory activity, higher than naproxen, a prescription drug reducing pain, swelling, and joint stiffness from arthritis[1].
IDO2-IN-1 (25, 50, 100 mg/kg; i.p.; once daily, for 19 d) exhibits excellent inhibitory effect on mice paw swelling, shows efficacy in a collagen-induced arthritis model in mice[1].
IDO2-IN-1 (30, 60, 120 mg/kg; i.p.; once daily, for 15 d) inhibits joint inflammation and displays potential effect in autoimmune arthritis improvement[1].
Pharmacokinetic Profile in Rat[1]
| Route | Dose (mg/kg) | T1/2/sub> (h) | Tmax (h) | Cmax (ng/mL) | AUC(0-∞) (h?ng/mL) | CL (mL/h/kg) | Vz (mL/kg) | MRT(0-∞) (h) | F (%) | | i.v. | 1 | 0.69 | / | / | 375.1 | 2673 | 2675 | 0.55 | / | | p.o. | 10 | 2.02 | 0.75 | 153.8 | 670.5 | / | / | 7.48 | 17.87 |
| Animal Model: | Xylene-induced ear swelling mouse model (ICR mice, male, 6 weeks old)[1] | | Dosage: | 100 mg/kg | | Administration: | Oral gavage; once dose; evenly coated right ear with 25 μL of xylene after 1 h treatment | | Result: | Significantly relieved mouse ear swelling with a high swelling inhibition rate of 65.32%.
|
| Animal Model: | Collagen-induced arthritis (CIA) mice model (DBA/1J mice, male, 6 weeks old)[1] | | Dosage: | 25, 50, 100 mg/kg | | Administration: | Intraperitoneal injection; once daily; 19 days, began on day 56 after collagen induced | | Result: | Decreased the expression of inflammatory cytokines IL-18 and IL-33.
Reduced inflammation and cartilage and bone erosions symptoms.
|
| Animal Model: | Adjuvant arthritis (AA) rat model (Sprague-Dawley rats, male, 180 ± 20 g)[1] | | Dosage: | 30, 60, 120 mg/kg | | Administration: | Intraperitoneal injection; once daily; 15 days, began on day 21 after chondrex induced | | Result: | Significantly reduced IL-6 and TNF-α levels.
Decreased synovial hyperplasia accompanied by inflammatory cell infiltration, pannus formation, and bone erosion of cartilage in a dose-dependent manner.
|
| [IC 50]
IDO1: 411 nM (IC50); IDO2: 112 (IC50) | [References]
[1] He G, et al. Discovery of the First Selective IDO2 Inhibitor As Novel Immunotherapeutic Avenues for Rheumatoid Arthritis. J Med Chem. 2022 Aug 11. DOI:10.1021/acs.jmedchem.2c00263 |
|
|