Preferred Label : PAI-1 Inhibitor ACT001;
NCIt synonyms : DMAMCL; Dimethylaminomicheliolide;
NCIt related terms : ACT-001;
NCIt definition : The fumarate salt form of the parthenolide derivative micheliolide (MCL), and an orally
bioavailable guaianolide sesquiterpene lactone and inhibitor of the protease plasminogen
activator inhibitor-1 (PAI-1), with potential immunomodulating and antineoplastic
activities. Upon oral administration, PAI-1 inhibitor ACT001 targets and binds to
PAI-1, thereby inhibiting the PAI-1/phosphoinositide 3-kinase (PI3K)/protein kinase
B (AKT) pathway. This induces apoptosis in and inhibits the proliferation, migration
and invasion of tumor cells in which the PI3K/AKT pathway is overexpressed. In addition,
ACT001 binds to and inhibits the activity of inhibitor of nuclear factor kappa-B kinase
subunit beta (IKK-beta), thereby inhibiting nuclear factor kappa B (NF-kB) signaling.
This leads to the downregulation of manganese superoxide dismutase (MnSOD) and induces
the generation of reactive oxygen species (ROS). This induces G2/M phase arrest and
tumor cell apoptosis. Also, ACT001 binds to and inhibits the phosphorylation of signal
transducer and activator of transcription 3 (STAT3), and reduces the expression of
programmed death-ligand 1 (PD-L1). This may modulate the anti-tumor immune response.
ACT001 may also affect tissue remodeling and cancer metabolism. PAI-1 plays a key
role in the proliferation, migration, invasion and adhesion of cancer cells as well
as multidrug resistance. It is highly expressed in certain tumors, such as gliomas.
ACT001 is able to cross the blood-brain barrier (BBB).;
UNII : 580BNQ45EO;
Molecule name : ACT-001; ACT 001;
NCI Metathesaurus CUI : CL1770633;
Origin ID : C182143;
UMLS CUI : C5565667;
Automatic exact mappings (from CISMeF team)
- Semantic type(s)
- UMLS correspondences (same concept)
- ACT001 [MeSH Supplementary Concept]
- concept_is_in_subset
- has_target
