Preferred Label : Anti-CD123/Kinesin Spindle Protein Inhibitor Antibody-drug Conjugate VIP943;
NCIt synonyms : Anti-CD123/KSPi ADC VIP943; Anti-CD123 Antibody-drug Conjugate VIP943; Anti-CD123 ADC VIP943;
NCIt definition : An antibody-drug conjugate (ADC) consisting of a monoclonal antibody against the interleukin-3
(IL3)-receptor alpha chain (CD123; IL-3RA), conjugated, via a legumain-cleavable linker,
to a physicochemically-modiffied payload composed of a kinesin spindle protein inhibitor
(KSPi), with potential antineoplastic activity. Upon administration of anti-CD123/KSPi
ADC VIP943, the antibody moiety targets the cell surface antigen CD123. Upon antibody/antigen
binding, internalization, and transport to the lysosome, the KSPi moiety is released
upon cleavage by the tumor-specific protease legumain, thereby accumulating the hydrophobic
KSP (kinesin-5 or Eg5) inhibitor inside the tumor cell. In turn, KSPi inhibits KSP,
thereby inhibiting mitotic spindle assembly, leading to an induction of cell cycle
arrest during the mitotic phase, and cell death in CD123-overexpressing tumor cells
that are actively dividing. This prevents proliferation of CD123-expressing tumor
cells. KSP is an ATP-dependent microtubule motor protein that is essential for the
formation of bipolar spindles and the proper segregation of sister chromatids during
mitosis. CD123 regulates the proliferation, survival and differentiation of hematopoietic
cells. CD123 is overexpressed on a variety of cancers, including myeloid leukemia,
and increased expression of CD123 on leukemic stem cells is associated with poor prognosis.
The modified KSPi payload is hydrophilic and thereby prevents diffusion out of the
cell, allowing intracellular accumulation and reduces off-target toxicities by preventing
membrane permeability into healthy cells.;
Molecule name : VIP-943; VIP 943;
NCI Metathesaurus CUI : CL1920702;
Origin ID : C201826;
UMLS CUI : C5907931;
Semantic type(s)
- concept_is_in_subset
- has_target
