Anti-TNFSF11 (Denosumab)-MC-Vc-PAB-MMAE ADC (ADC-W-2237)

 ADC Target

  • Name
  • TNFSF11
  • Alternative Names
  • TNFSF11; tumor necrosis factor (ligand) superfamily, member 11; tumor necrosis factor ligand superfamily member 11; CD254; ODF; OPGL; RANKL; TRANCE; osteoprotegerin ligand; osteoclast differentiation factor; TNF-related activation-induced cytokine; receptor activator of nuclear factor kappa B ligand; receptor activator of nuclear factor kappa-B ligand; sOdf; OPTB2; hRANKL2;
  • Target Entrez Gene ID
  • 8600
  • Overview
  • This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found.

 ADC Antibody

  • Overview
  • Human Anti-TNFSF11 IgG2 antibody, Denosumab
  • Generic name
  • Denosumab
  • Host animal
  • Human

 ADC Linker

  • Name
  • MC-Vc-PAB (maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl)
  • Description
  • Peptide linkers, belonging to Enzymatically cleavable linkers, combine greater systemic stability with rapid enzymatic release of the drug in the target cell. The scission of peptidic bonds relies on lysosomal proteolytic enzymes, which have very low activities in blood due to endogenous inhibitors and the unfavorably high pH value of blood.

 ADC payload drug

  • Name
  • MMAE
  • Description
  • Derived from Auristatin,are water-soluble dolastatin analogs of dolastatin 10. Dolastatin 10 belongs to dolastatin family and it can powerfully bind to tubulin, thus inhibiting polymerization mediated through the binding to the vinca alkaloid binding domain, and causes cell to accumulate in metaphase arrest.

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