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Natalizumab, a recombinant, humanized antibody, binds to α4β1-integrin and blocks its interaction with VCAM-1. As a result, leukocyte migration into brain tissue is inhibited, reducing inflammation and preventing the formation of lesions. Natalizumab may also inhibit ongoing central nervous system (CNS) inflammation, mediated by leukocytes already present in the CNS, by interrupting the interactions between α4-integrin-expressing leukocytes and extracellular matrix proteins such as fibronectin and osteopontin.

Natalizumab binds rapidly and with high affinity to α4-integrin. Maximal binding (≥80% saturation), measured in vitro on isolated lymphocyte membranes, occurred 24 hours after intravenous (IV) doses of natalizumab 1 mg/kg to 6 mg/kg.