Preferred Label : Letolizumab;
NCIt synonyms : Fc-Fusion Protein BMS986004;
NCIt definition : A dimeric fusion protein composed of the C-terminus of the domain antibody (dAb) BMS2h-572-633
targeting the CD40 ligand (CD40L or CD154) linked to a modified Fc fragment of immunoglobulin
G1 (IgG1), with potential immunomodulatory activity. Upon intravenous administration,
the peptide moiety of letolizumab specifically targets and binds to CD40L expressed
on T-lymphocytes. This prevents the binding of CD40L to its cognate receptor CD40
expressed on B-lymphocytes, macrophages, and dendritic cells (DCs). This prevents
T-cell mediated proliferation and differentiation of B-cells, and prevents the production
of antibodies. By inhibiting both the production of anti-glycoprotein (GP) IIb/IIIa
antibodies by B-cells and GPIIb/IIIa-dependent T-cell proliferation, letolizumab may
prevent platelet destruction and may increase platelet counts in idiopathic thrombocytopenic
purpura (ITP). The direct binding of letolizumab to CD40L on platelets further prevents
CD40L/CD40-mediated destruction by macrophages and DCs in ITP. The modified Fc domain
prevents the binding of letolizumab to the Fc receptor FcgammaRIIA on platelets, thereby
preventing FcgammaRIIA-dependent platelet activation and anti-CD40L-induced thromboembolism.
CD40L, a transmembrane protein of the tumor necrosis factor (TNF) superfamily, is
primarily expressed on activated T-cells, but is also expressed on eosinophils, basophils,
natural killer (NK) cells, mast cells, platelets and activated endothelial cells.;
UNII : 449MIE2SD6;
CAS number : 1450981-87-9;
Molecule name : BMS-986004;
Origin ID : C120140;
UMLS CUI : C5239412;
Semantic type(s)
- concept_is_in_subset
- has_target
