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- NCIT_C65876 IAO_0000115 "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." @default.
- NCIT_C65876 NCIT_NHC0 "C65876" @default.
- NCIT_C65876 NCIT_P106 "Pharmacologic Substance" @default.
- NCIT_C65876 NCIT_P107 "Ibudilast" @default.
- NCIT_C65876 NCIT_P108 "Ibudilast" @default.
- NCIT_C65876 NCIT_P207 "C0123047" @default.
- NCIT_C65876 NCIT_P210 "50847-11-5" @default.
- NCIT_C65876 NCIT_P319 "M0TTH61XC5" @default.
- NCIT_C65876 NCIT_P322 "CTRP" @default.
- NCIT_C65876 NCIT_P322 "FDA" @default.
- NCIT_C65876 NCIT_P329 "796798" @default.
- NCIT_C65876 NCIT_P330 "796798" @default.
- NCIT_C65876 NCIT_P350 "C14H18N2O" @default.
- NCIT_C65876 NCIT_P366 "Ibudilast" @default.
- NCIT_C65876 NCIT_P399 "796798" @default.
- NCIT_C65876 normalizedInformationContent "100" @default.
- NCIT_C65876 referenceCount "1" @default.
- NCIT_C65876 hasExactSynonym "3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine" @default.
- NCIT_C65876 hasExactSynonym "IBD" @default.
- NCIT_C65876 hasExactSynonym "IBUDILAST" @default.
- NCIT_C65876 hasExactSynonym "Ibudilast" @default.
- NCIT_C65876 hasExactSynonym "MN-166" @default.
- NCIT_C65876 inSubset NCIT_C116977 @default.
- NCIT_C65876 inSubset NCIT_C116978 @default.
- NCIT_C65876 inSubset NCIT_C173381 @default.
- NCIT_C65876 inSubset NCIT_C173383 @default.
- NCIT_C65876 inSubset NCIT_C176424 @default.
- NCIT_C65876 inSubset NCIT_C63923 @default.
- NCIT_C65876 type Class @default.
- NCIT_C65876 isDefinedBy ncit.owl @default.
- NCIT_C65876 label "Ibudilast" @default.
- NCIT_C65876 subClassOf NCIT_C1327 @default.
- NCIT_C65876 subClassOf NCIT_C1908 @default.
- NCIT_C65876 subClassOf NCIT_C1909 @default.
- NCIT_C65876 subClassOf NCIT_C29707 @default.
- NCIT_C65876 subClassOf NCIT_C65876 @default.
- NCIT_C65876 subClassOf NCIT_C78274 @default.
- NCIT_C65876 subClassOf NCIT_C78275 @default.