Preferred Label : Anti-mutant Calreticulin Monoclonal Antibody INCA033989;
NCIt synonyms : Anti-mutCALR Monoclonal Antibody INCA033989; Anti-mutant CALR Monoclonal Antibody INCA033989;
NCIt definition : A human immunoglobulin G1 (IgG1) monoclonal antibody targeting the mutated form of
calreticulin (mutCALR), with potential antineoplastic activity. Upon administration,
anti-mutCALR monoclonal antibody INCA033989 selectively targets and binds to mutCALR
expressed on CALR mutated CD34-positive hematopoietic stem cells (HSCs) while not
binding to normal wild-type (WT) CALR on healthy CD34-positive HSCs. This prevents
the formation of a mutCALR complex with the thrombopoietin receptor (TPO-R) in the
endoplasmic reticulum (ER), prevents the CALR mutant-dependent TPO-R dimerization
and suppresses TPO-R signaling. This prevents the activation of the downstream Janus
kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling
pathway. This prevents mutCALR-driven oncogenic cell proliferation, causes cell cycle
arrest and induces cell death. CALR mutations, either insertions or deletions in exon
9, result in a frameshift that causes the loss of the KDEL ER retention motif. CALR
mutations drive a variety of myeloproliferative neoplasms (MPNs).;
Molecule name : INCA 033989; INCA-033989;
Origin ID : C201954;
chemical_or_drug_has_mechanism_of_action
- concept_is_in_subset
- has_target
