IDO2-IN-1 (C09-1140-397)

IDO2-IN-1 is an orally active and potent Indoleamine 2,3-dioxygenase 2 ( IDO2 ) inhibitor with an IC 50 value of 112 nM. IDO2-IN-1 can be used for inflammatory autoimmunity researchIn VitroIDO2-IN-1 (compound 22) shows stronger inhibition on IDO2 (IC 50 =112 nM) over IDO1 (IC 50 =411 nM). IDO2-IN-1 inhibits hIDO1 expression (EC 50 =633 nM) in HeLa cell-based IDO1/kynurenine assay, co-incubated with hIFN-γ (100 ng/mL final concentration), which is used for producing N-formylkynurenine. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: HeLa cells line expressing hIDO1 induced by IFN-γ Concentration: 1 nM-0.1 mM Incubation Time: 48 hours Result: Showed additional potency against IDO1 with an EC 50 value of 633 nM.In VivoThe 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 . 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 . 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 . Pharmacokinetic Profile in Rat Route Dose (mg/kg) T 1/2/sub> (h) T max (h) C max (ng/mL) AUC (0-∞) (h•ng/mL) CL (mL/h/kg) V z (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 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Xylene-induced ear swelling mouse model (ICR mice, male, 6 weeks old) 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) 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) 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.Form:SolidIC50& Target:IDO1 411 nM (IC 50 ) IDO2 112 (IC 50 ). Specification: 0.98 Molecular Formula: C21H21BrN10O3 Molecular Weight: 541.36