Ask about this productRelated genes to: PDE4B antibody
- Gene:
- PDE4B NIH gene
- Name:
- phosphodiesterase 4B
- Previous symbol:
- DPDE4
- Synonyms:
- -
- Chromosome:
- 1p31.3
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-29
- Date modifiied:
- 2016-10-05
Related products to: PDE4B antibody
Related articles to: PDE4B antibody
- The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is a robust, rapid-acting antidepressant whose molecular effects have not been fully elucidated. Phosphodiesterase-4 (PDE4), which terminates cyclic adenosine monophosphate (cAMP) activity, may underlie antidepressant response. In particular, previous studies found that whole brain binding of the positron emission tomography (PET) radioligand [C](R)-rolipram to PDE4 was decreased in individuals with major depressive disorder; eight weeks of antidepressant treatment rescued this decrease in [C](R)-rolipram binding. This study used [C](R)-rolipram, which targets all PDE4 subtypes, and [F]PF-06445974, which is preferential for PDE4B over PDE4D, to determine whether ketamine infusion could rapidly increase cAMP activity in rats (at 10 mg/kg) and rhesus macaques (at 0.5 mg/kg). Ketamine increased [C](R)-rolipram binding to PDE4 in rats (mean standardized uptake value (SUV) increase=24% ± 14%, range=3%-42%, p = 0.004) and in monkeys (mean distribution volume (V) increase=14% ± 2%, range=12%-16%, p = 0.003). Ketamine also increased [F]PF-06445974 binding in monkeys within one hour of infusion (mean V increase 28% ± 7%, range=16%-37%, p = 0.008). When [C](S)-rolipram, which has no specific binding to PDE4, was used to control for the effects of ketamine on blood flow and radioligand delivery in rats, no consistent effects were observed for ketamine. Collectively, the results suggest that ketamine infusion rapidly increases cAMP activity and may be an underlying mechanism for ketamine's rapid antidepressant effects. These data support a common pathway for cAMP and antidepressant action and suggest that PDE4 inhibition, particularly PDE4B, may be an effective and rapid-acting antidepressant mechanism. - Source: PubMed
Publication date: 2026/04/21
Parcon Paul ABardhoshi AmandaOlsen-Dufour AmandaCureton RavenJana SusovanMorse Cheryl LHenter Ioline DTotis JuliaJenson Adrian EPamie-George Matilah TLiow Jeih-SanZoghbi Sami SWu ShawnPike Victor WInnis Robert B - - Source: PubMed
Publication date: 2026/04/10
Mohamed Soad AAbdelgawad Mohamed AAlaeddin RaniaHisham MohamedSaber Entesar AliNayl Abdelaziz ASelim SamyAbdel-Aziz MohamedHayallah Alaa MElrehany MahmoudZahran Eman Maher - When tumor cells colonize distant organs during metastasis, they interact extensively with surrounding cells. These interactions often change the behavior of surrounding cell populations which collectively induce a protumor microenvironment that permits tumor cell outgrowth into overt, clinically detectable metastatic disease. The lung is one of the most common sites of breast cancer metastasis. A chronic wound repair-related phenotype developed within the lung microenvironment during metastatic outgrowth in immunocompetent preclinical mouse models of breast cancer. This phenotype was characterized by an increased number and activation of lung type II alveolar epithelial (AT2) cells surrounding growing metastases. Metastatic outgrowth significantly changed AT2 gene expression, resulting in a modified secretome. AT2-derived secreted factors also promoted triple-negative breast cancer growth. AT2-secreted factors are regulated by the cyclic adenosine monophosphate response element-binding protein (CREB). Targeting CREB signaling with the phosphodiesterase 4 (PDE4) inhibitor roflumilast reduced AT2 breast cancer reciprocal interactions in vitro and metastatic outgrowth in vivo. Finally, AT2 cells adjacent to metastases in lungs from patients with metastatic breast cancer expressed higher PDE4B compared with AT2 cells in normal lungs. - Source: PubMed
Publication date: 2026/03/10
Christenson Jessica LSpoelstra Nicole SWilliams Michelle MLogan Linda LO'Neill Kathleen IOrlicky David JBaker Nolan TWagner Jennifer AStaley Alyse WVan Bokhoven AdrieGoodspeed AndrewKuo Li-WeiCrump Lyndsey SDiamond Jennifer RRicher Jennifer K - Phosphodiesterase 4B (PDE4B), an isoform of cyclic nucleotide phosphodiesterases, is integrated into cell membranes and hydrolyzes cyclic AMP in specific cellular compartments. Overexpression of PDE4B has been observed in hematological and gastrointestinal tumors harboring KRAS mutations, leading to the disruption of cell cycle regulation. Utilizing molecular docking, we identified 3-aminoisoquinolines as potential selective PDE4B inhibitors. Phenotypic screening on HKe3-KRAS cell lines confirmed that PDE4B is a selective target for these novel 3-aminoisoquinolines. We employed molecular docking and calculated ligand efficiency as predictive tools for methylthiazoltetrazolium assay activity to reduce the combinatorial library size. Six active compounds (047, 048, 086, 089, 091, and 099) were screened. Active compounds 047, 048, 086, 089, and 091 demonstrated selectivity toward HKe3-mtKRAS over wild-type cells. This 'synthetic lethality-like' approach was effective in predicting the anticancer properties of these compounds in KRAS-mutated cell lines. NCI-DTP 60 cell lines assays confirmed the activities of 047, 048, and 089. Compound 089 showed strong cytotoxicity against HCT-116 cells inhibitory concentration (IC50) = 1.6 μM, growth inhibition (GI50) = 0.53 μM, and an inhibitory concentration (IC50) against PDE4B = 2.5 μM. In addition, 089 exhibited good tolerability in a nude mouse HCT-116 xenograft model, but it was less effective at a dose of 40 mg/kg compared with Apremilast at a dose of 30 mg/kg in 8-s day's assay. While 089 had lower in-vivo efficacy than apremilast, its novel 3-aminoisoquinoline scaffold and high tolerability make it a superior candidate for further optimization. - Source: PubMed
Publication date: 2026/03/10
Lapa Gennady BTsunoda ToshiyukiMoiseeva Natalia I - Idiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal lung disease with a poor prognosis. BI-1015550 is an oral phosphodiesterase 4B (PDE4B) inhibitor that has shown anti-inflammatory and anti-fibrotic effects; the exact molecular target(s) and mechanism of action in fibrosis are unknown. BI-1015550, an orally available PDE4B inhibitor with a possible anti-fibrotic effect, whose molecular mechanism of action is unknown Methods: We adopt an integrative approach that combines network pharmacology for identifying putative targets, molecular docking, and Molecular Dynamics (MD) simulations to assess the binding, ML-based target prioritization. Predicted targets/pathways were verified by Western blotting and Immunohistochemistry (IHC). - Source: PubMed
Publication date: 2026/03/31
Jiao LiyuanZhang Caiqing