drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
An antibody–drug conjugate consisting of a pH-dependent anti-cMET monoclonal antibody linked to the antimicrotubule payload monomethyl auristatin E (MMAE). It binds c-MET on tumor cells, is internalized, and releases MMAE in acidic compartments to disrupt microtubules and induce G2/M arrest and apoptosis.
nci_thesaurus_concept_id
C199255
nci_thesaurus_preferred_term
Anti-c-Met/MMAE ADC MYTX-011
nci_thesaurus_definition
An antibody-drug conjugate (ADC) composed of an engineered pH-dependent humanized immunoglobulin G1 (IgG1) monoclonal antibody against the tumor-associated antigen (TAA) proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) and conjugated, via a valine-citrulline (VC) peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon intravenous administration of anti-c-Met/MMAE ADC MYTX-011, the monoclonal antibody moiety targets and binds to c-Met expressed on tumor cells. Upon binding, internalization, and proteolytic cleavage, MMAE is released. MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. This induces cell death in c-Met-expressing cancer cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis. The engineered pH-dependent anti-c-Met antibody allows enhanced binding and thus uptake into c-Met-expressing cancer cells while reducing binding to and uptake in healthy cells. This may increase efficacy and improve tolerability.
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
MYTX-011 is an anti-c-MET monoclonal antibody-drug conjugate linked via a cleavable valine-citrulline linker to the microtubule inhibitor MMAE. After binding c-MET on tumor cells, the complex is internalized and MMAE is released in acidic compartments, where it inhibits tubulin polymerization, leading to microtubule disruption, G2/M cell-cycle arrest, and apoptosis. The pH-dependent antibody design enhances tumor-selective uptake and may improve tolerability.
drug_name
MYTX-011
nct_id_drug_ref
NCT05652868