DL-404

DL-404 (also known as DS-1211) is an orally bioavailable, small-molecule inhibitor of tissue-nonspecific alkaline phosphatase (TNAP) developed by Daiichi Sankyo. TNAP is an enzyme that plays a critical role in bone mineralization by hydrolyzing inorganic pyrophosphate (PPi), which is a natural inhibitor of hydroxyapatite crystal formation. In pathological conditions such as pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), low systemic levels of PPi lead to ectopic calcification in soft tissues, including the skin, eyes, and cardiovascular system. By inhibiting TNAP, DL-404 aims to increase systemic PPi levels, thereby preventing or reducing the progression of pathological calcification. The drug is currently being evaluated in Phase 2 clinical trials for PXE and other ectopic calcification disorders.