HB1148 (Haisco Pharmaceutical Group Co., Ltd.)

HB1148 is a potent, highly selective, allosteric inhibitor of Tyrosine Kinase 2 (TYK2) currently under development by Haisco Pharmaceutical Group. As a member of the Janus kinase (JAK) family, TYK2 plays a critical role in the signaling pathways of pro-inflammatory cytokines such as interleukin-23 (IL-23), interleukin-12 (IL-12), and Type I interferons (IFN). Unlike traditional JAK inhibitors that target the highly conserved orthosteric ATP-binding site (JH1 domain), HB1148 binds to the regulatory pseudokinase (JH2) domain. This allosteric mechanism allows for exceptional selectivity for TYK2 over JAK1, JAK2, and JAK3, potentially avoiding the safety concerns associated with pan-JAK inhibition, such as hematological toxicities and cardiovascular events. HB1148 is primarily being evaluated for the treatment of moderate-to-severe plaque psoriasis, with potential applications in other immune-mediated inflammatory diseases like Crohn's disease and systemic lupus erythematosus.