Ivarmacitinib

Ivarmacitinib (SHR0302) is a potent and orally active all members of the JAK family inhibitor, particularly JAK1. The selectivity of Ivarmacitinib for JAK1 is >10-fold for JAK2, 77-fold for JAK3, 420-fold for Tyk2. Ivarmacitinib inhibits JAK1-STAT3 phosphorylation and induces the apoptosis of hepatic stellate cells. Ivarmacitinib has anti-proliferative and anti-inflammatory effects^[1][2]. In Vitro:Ivarmacitinib (SHR0302; 1 nM-10 µM; 48 hours; HSCs) treatment displays an inhibitory effect on the proliferation of HSCs in a concentration-dependent manner^[2].
Ivarmacitinib (1 nM-10 µM) exerts an inhibitory effect on the activation, proliferation and migration of HSCs^[2].
Ivarmacitinib (1 nM-10 µM; 48 hours; HSCs) treatment induces the apoptosis of HSCs^[2].
Ivarmacitinib (1 nM-10 µM; 48 hours; HSCs) treatment significantly increases the activation of caspase-3 and Bax in HSCs, and decreases the expression of Bcl-2. SHR0302 also inhibits the activation of Akt signaling pathway^[2]. In Vivo:Ivarmacitinib (SHR0302; 0.3-3.0 mg/kg; intragastric administration; twice a day; for 14 days; male Sprague-Dawley (SD) rats) treatment suppresses the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats^[1].
Ivarmacitinib can inhibit the proliferation of T, B and fibroblast-like synoviocytes (FLS), and down-regulates cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppresses the proportion of Th17 and total B, and inhibits JAK1-STAT3 phosphorylation^[1].