IA-14069

IA-14069 is an orally active tumor necrosis factor-α ( TNF-α ) inhibitor. IA-14069 binds directly to TNF-α and TNF-α-triggered signaling (p-IκBα and NF-κB p65) activities. Additionally, IA-14069 exerts a suppressive effect on Dextran sodium sulfate (DSS)-induced colitis. IA-14069 can be used for the research of Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) ^{[1] [2]}.

In Vivo, IA-14069 (3.3-33 mg/kg twice per week or 25-100 mg/kg 3 times per week, p.o.) exhibits both preventive and therapeutic anti-rheumatoid arthritis effects respectively in TNF-α-transgenic (TNF-α-TG) models^[1]. IA-14069 (25 mg/kg, 3 times per week, p.o.) exhibits therapeutic anti-rheumatoid arthritis effects in collagen-induced arthritis (CIA) models^[1]. IA-14069 (10 mg/kg, 3 times per week, p.o.) exerts synergistic effects with Methotrexate (MTX, 5 mg/kg, 3 times per week, p.o.) in the CIA therapeutic model^[1]. IA-14069 exhibits significant bioavailability and shows no in vivo toxicity even at excessive doses^[1]. IA-14069 (20-160 mg/kg, daily for 5-12 days, p.o.) exerts a suppressive effect on DSS-induced colitis^[2].

In Vitro, IA-14069 potently inhibits both TNF-α-induced cytotoxicity (IC₅₀ < 0.7 μM), which directly binds to TNF-α and TNF-α-triggered signaling (p-IκBα and NF-κB p65) activities^[1].

References:
[1]. Park S, et al. THU0047 IA-14069, A NOVEL SMALL-MOLECULE INHIBITOR DIRECT-TARGETING TUMOR NECROSIS FACTOR-α, ATTENUATES COLLAGEN INDUCED ARTHRITIS. Annals of the Rheumatic Diseases. 2019, 78:291
[2]. Okki Cho, et al. TNF targeting small molecule attenuates colonic inflammation in acute DSS-induced colitis mice. The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 52.11