TK22

TK22 is a novel, reversible small molecule inhibitor of cyclin-dependent kinase 5 (CDK5). It is being investigated for its potential to treat pulmonary arterial hypertension (PAH) and other vascular pathologies by targeting the endothelial-to-mesenchymal transition (EndMT). In preclinical studies, TK22 has demonstrated the ability to reduce the expression of mesenchymal markers (such as αSMA, SM22α, and Calponin) induced by TGF-β1, restore angiogenic potential, and reduce cell proliferation and collagen contraction. By inhibiting the CDK5 signaling pathway, TK22 aims to halt or reverse the phenotypic shift of endothelial cells into mesenchymal-like cells, thereby addressing vascular remodeling.