LY-364947 and HTS 466284 are selective inhibitors of the TGF-β (transforming growth factor-beta) receptor kinase, particularly targeting TGF-β type I receptor (ALK5). These compounds are widely used in research to block TGF-β signaling pathways, which play key roles in cell proliferation, differentiation, apoptosis, and immune regulation. One major application is in cancer research, where inhibition of TGF-β signaling helps counteract tumor progression and metastasis. In many cancers, TGF-β promotes epithelial-to-mesenchymal transition (EMT), a process linked to increased invasiveness. By blocking ALK5, these inhibitors reduce EMT and may restore sensitivity to other anticancer therapies. They are also used in fibrosis studies. Excessive TGF-β activity contributes to tissue scarring in organs such as the liver, lungs, and kidneys. LY-364947 and HTS 466284 have shown efficacy in reducing collagen deposition and fibroblast activation in preclinical models, making them valuable tools for testing antifibrotic strategies. In immunology, these inhibitors help modulate immune responses. TGF-β is a potent immunosuppressor, and its inhibition can enhance T-cell activation and reduce regulatory T-cell function, which is relevant in vaccine development and immunotherapy. Overall, these compounds serve as critical pharmacological tools for dissecting TGF-β-dependent processes and evaluating therapeutic interventions in cancer, fibrosis, and immune disorders.