Preferred Label : Ibudilast;
NCIt synonyms : 3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine; IBD;
NCIt definition : An orally bioavailable inhibitor of cyclic nucleotide phosphodiesterase (PDE), mainly
PDE-3, -4, -10, and -11, with anti-(neuro)inflammatory, vasorelaxant, bronchodilator,
analgesic, neuroprotective and potential anti-tumor activities. Ibudilast (IBD) is
able to cross the blood-brain barrier (BBB). Upon administration, IBD exerts its potential
anti-tumor activity against glioblastoma multiforme (GBM) cells by inhibiting PDE-4
and the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which
results in a decrease in MIF, its receptor CD74, and AKT expression, and attenuates
the immunosuppressive properties of monocytic myeloid-derived suppressor cells (MDSCs)
and reduces T-regulatory cells (Tregs). This causes GBM cell apoptosis and inhibits
GBM cell proliferation. In addition, IBD reduces, through its inhibitory effect on
various PDEs, the production of certain pro-inflammatory cytokines, such as interleukin-6
(IL-6), IL- 1beta, leukotriene B4, and tumor necrosis factor-alpha (TNF-a). IBD also
upregulates the anti-inflammatory cytokine (IL-10), and promotes the production of
neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), nerve growth
factor (NGF), and neurotrophin-4 (NT-4). It also blocks toll-like receptor-4 (TLR-4),
inhibits nitric oxide (NO) synthesis and reduces the level of reactive oxygen species
(ROS). It also prevents platelet aggregation, causes cerebral vasodilation, bronchial
smooth muscle relaxation, and improves cerebral blood flow. In addition, IBD attenuates
the PDE-mediated activation of glial cells and abrogates PDE-mediated neuroinflammation
and neurodegeneration. MIF is secreted by cancer stem cells (CSCs) and is highly expressed
within GBM and plays a key role in tumor cell proliferation. Co-expression of MIF
and CD74 in GBM is associated with poor patient survival.;
UNII : M0TTH61XC5;
InChIKey : ZJVFLBOZORBYFE-UHFFFAOYSA-N;
CAS number : 50847-11-5;
Molecule name : MN-166;
Chemical formula : C14H18N2O;
Origin ID : C65876;
UMLS CUI : C0123047;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to BTNT
- concept_is_in_subset
