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Biological and Environmental Research Ontology
| Id | http://purl.obolibrary.org/obo/NCIT_C120140
http://purl.obolibrary.org/obo/NCIT_C120140
|
|---|---|
| Preferred Name | Letolizumab |
| Definitions |
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.
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| Type | http://www.w3.org/2002/07/owl#Class |
All Properties
| 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. |
|---|---|
| prefLabel | Letolizumab
|
| label | Letolizumab
|
| PDQ_Closed_Trial_Search_ID | 773819
|
| code | C120140
|
| Has_Target | |
| prefixIRI | NCIT:C120140
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| in_subset |
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| Display_Name | Letolizumab
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| Preferred_Name | Letolizumab
|
| FDA_UNII_Code | 449MIE2SD6
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| Contributing_Source |
CTRP
FDA
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| Maps_To |
Anti-CD40L Fc-Fusion Protein BMS-986004
Letolizumab
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| CAS_Registry | 1450981-87-9
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| NCI_Drug_Dictionary_ID | 773819
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| type | |
| Is_Value_For_GDC_Property | |
| subClassOf | |
| PDQ_Open_Trial_Search_ID | 773819
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| Semantic_Type | Pharmacologic Substance
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| UMLS_CUI | C3896896
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