Natalizumab (Anti-CD49d)

Natalizumab (Anti-CD49d) (AN100226; BG00002) Solution is a humanized monoclonal IgG4 antibody inhibitor that selectively targets α4 integrin (CD49d), blocking the interaction of integrins such as α4β1 (VLA-4) with vascular cell adhesion molecule VCAM-1, intercellular adhesion molecule ICAM-1, and fibronectin by competitively binding to the α4 subunit. Natalizumab solution inhibits the adhesion, retention, and transendothelial migration of immune cells (such as CD4⁺ T cells), reducing the infiltration of inflammatory cells into the central nervous system or lesion sites, thereby exerting anti-inflammatory and immunomodulatory activity. Natalizumab (Anti-CD49d) solution is used in the study of relapsing-remitting multiple sclerosis (RRMS) and is also applied in the research of autoimmune or inflammation-related diseases such as Crohn's disease, B-cell lymphoma, and non-infectious uveitis. Natalizumab (Anti-CD49d) can also prevent lymphocytes from entering the central nervous system, thus preventing acute demyelinating relapses^{[1][2][3][4][5]}. IC50 & Target:ITGA4 In Vitro: Natalizumab (Anti-CD49d) (10 μg/mL, 2 h) reduced the adhesion of VLA-4-positive lymphoma cells (Raji, Karpas-422, etc.) to fibronectin by 75-95% and altered cell adhesion morphology^[2].
Natalizumab (Anti-CD49d) (10 μg/mL in combination with rituximab) partially overcame the protective effect of bone marrow stromal cells on lymphoma B cells, mitigating resistance to apoptosis induced by Rituximab (HY-P9913) and cytotoxic drugs^[2].
Natalizumab (Anti-CD49d) (30 μg/mL) slightly upregulated the expression of IL-2, IFN-γ, and IL-17 in activated CD4⁺ T cells, triggered MAPK/ERK phosphorylation, and downregulated CD49d surface expression^[3].
Natalizumab (Anti-CD49d) (1 μg/mL) alone could not significantly inhibit the retention of CD4⁺ T cells or PBMCs in an inflammatory state BBB model (BLEC, HBMEC, etc.), requiring co-inhibition of β2-integrin for complete blockade^[1].
Natalizumab (Solution) (1 μg/mL) was ineffective in inhibiting shear-resistant retention of CD4⁺ Th1 cells when the molar ratio of ICAM-1 to VCAM-1 was 10:1^[1].
In Vivo: Natalizumab (Anti-CD49d) (170 μg/mouse; intravenous injection; single dose) significantly inhibited the firm adhesion of human T cells to the blood-brain barrier (BBB) under inflammatory conditions in an experimental autoimmune encephalomyelitis (EAE) model in female SJL mice, without affecting T cell rolling or capture, and the inhibitory effect lasted for 120 minutes^[4].
Natalizumab (Anti-CD49d) (170 μg/mouse; intravenous injection; single dose) only partially and transiently reduced the firm adhesion of human T cells to the activated BBB in a TNF-α-induced acute systemic inflammation model in female SJL mice, significantly reducing T cell rolling along the vessel wall but not affecting capture^[4].
Natalizumab (Solution) (0.625-2.5 mg/mouse; intravitreal injection; single dose; 21-day observation period) showed no functional or structural toxicity to the retina of New Zealand white rabbits at doses of 0.625-1.25 mg, with no significant changes in the amplitude and latency of a-wave and b-wave in electroretinogram (ERG), but the 2.5 mg dose caused retinal dysfunction, with significantly reduced a-wave and b-wave amplitudes in ERG, and ultrastructural damage in the outer plexiform layer and inner nuclear layer^[5].