AZD-1480 JAK2 inhibitor
- Known as:
- AZD-1480 JAK2 suppressor
- Catalog number:
- a-1135
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- ActivBio Active Biochem
- Gene target:
- AZD-1480 JAK2 inhibitor
Related genes to: AZD-1480 JAK2 inhibitor
- Gene:
- JAK2 NIH gene
- Name:
- Janus kinase 2
- Previous symbol:
- -
- Synonyms:
- JTK10
- Chromosome:
- 9p24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1992-04-16
- Date modifiied:
- 2019-04-23
Related products to: AZD-1480 JAK2 inhibitor
Related articles to: AZD-1480 JAK2 inhibitor
- Spinal cord injury (SCI) leads to irreversible neurological deficits primarily through secondary injury mechanisms, including oxidative stress and glial dysfunction. Sulforaphane (SFN), a naturally occurring isothiocyanate, has shown antioxidant and anti-inflammatory effects in various neurological models, but its impact on Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and microglial polarization in SCI remains unclear. Adult male Wistar rats were randomly assigned to Sham, SCI, or SCI + SFN groups (n = 10/group). SCI was induced by a moderate T10 contusion, and SFN (50 mg/kg, i.p.) was administered at 10 min, 72 h, and 7 days post-injury. Locomotor recovery was assessed using the Basso-Beattie-Bresnahan (BBB) scale. At day 14, spinal cord tissue was analyzed for oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), as well as JAK2/STAT3 signaling and microglial polarization. SCI significantly increased ROS and MDA levels while reducing SOD activity and GSH content. Phosphorylation of JAK2 and STAT3, along with glial fibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), was markedly elevated. SFN treatment restored antioxidant defenses, suppressed JAK2/STAT3 activation, partially recovered suppressor of cytokine signaling 3 (SOCS3), and reduced pro-inflammatory responses. Moreover, SFN shifted microglial polarization from a pro-inflammatory (M1) toward a reparative (M2) phenotype and significantly improved BBB locomotor scores compared with untreated SCI rats. SFN confers neuroprotection in SCI by reducing oxidative stress, modulating JAK/STAT signaling, rebalancing microglial polarization, and improving locomotor recovery. These findings highlight SFN as a promising candidate for therapeutic development in SCI. - Source: PubMed
Publication date: 2026/05/28
Saeed Zainab HameedWeshel Widyan GataaLafta Ali HusseinAmeen Murtadha AzeezAbbass Zainab HannonAkhtam AkramovAxmedov Shamshod - Colorectal cancer (CRC) remains difficult to treat due to challenges in early detection and the development of therapeutic resistance. Dopamine receptor D2 (DRD2) plays a critical role in regulating cell proliferation and apoptosis in various solid tumors. Given the relatively high levels of dopamine in the gastrointestinal tract, colorectal tumors may be particularly susceptible to DRD2-mediated signaling. In this study, we evaluated the anticancer activity of a newly synthesized DRD2 antagonist, SD2-2305, and investigated its underlying mechanisms in human CRC cell lines HCT116 and HT-29. SD2-2305 reduced cell viability in a time- and dose-dependent manner. Induction of apoptosis was confirmed by Annexin V/PI staining and immunoblot analysis, with activation of caspase-3, caspase-7, and caspase-9, although no significant changes were observed in the expression of Bcl-2 family proteins. Furthermore, SD2-2305 induced G1 phase cell cycle arrest, accompanied by downregulation of Cyclin A, Cyclin B, CDK1, and CDK2, and upregulation of p21. While key survival pathways (JAK2/STAT3, PI3K/Akt, and MAPK) remained relatively unaffected, SD2-2305 modulated growth factor receptors post-transcriptionally, decreasing HER2/ErbB2 and increasing TGF-beta receptor 1 expression. Collectively, these findings demonstrate that the DRD2 antagonist SD2-2305 exerts potent anticancer effects through the induction of cell cycle arrest and apoptosis, and suggest that the anticancer activity of SD2-2305 is associated with coordinated modulation of growth factor receptor signaling and cell-cycle regulators in CRC cells. - Source: PubMed
Publication date: 2026/06/30
Kim Na HyunCho Geun YoungKim In-TaeChoi You-JinPark KeunwanKang KyungsuChoi Joon-SeokLee Sujin - Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury. - Source: PubMed
Publication date: 2026/06/30
Yang JingjingLing ZhiZhou MingTao MingyangMao JingxianGuo HuaijuanWang JiaxinQu XiaoWang YingZhu YefeiZhang KunYan Xuebing - To investigate the effect of S100A4 on pulmonary fibrosis and elucidate its underlying mechanism involving the long non-coding RNA MEG3 (lncRNA MEG3) /microRNA-147 (miR-147) pathway. In November 2024, a model of S100A4-overexpressing mouse alveolar macrophages (MH-S cells) was established. A Transwell co-culture system was set up with mouse lung fibroblasts. The control group consisted of MH-S cells transfected with an empty plasmid co-cultured with mouse lung fibroblasts, while the transfection group consisted of S100A4-overexpressing MH-S cells co-cultured with mouse lung fibroblasts. The S100A4 level in the supernatant was detected by western blotting. The proliferation activity of co-cultured mouse lung fibroblasts was measured by CCK-8 assay. Cell cycle distribution was analyzed by PI staining flow cytometry, and the apoptosis rate was determined by Annexin V-FITC/PI double staining flow cytometry. Cell migration ability was assessed using Transwell chambers. Western blotting was employed to detect S100A4 expression in MH-S cells, as well as the expressions of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) in mouse lung fibroblasts. Quantitative real time polymerase chain reaction (qPCR) was used to measure the levels of LncRNA MEG3, miR-147, and α-smooth muscle actin (α-SMA) mRNA. Immunofluorescence was used to detect α-SMA protein expression. The levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). All results were normally distributed measurement data, and comparisons between groups were performed using one way analysis of variance (ANOVA) . Compared with the control group, the transfection group exhibited a significantly increased S100A4 level in the supernatant. In mouse lung fibroblasts co-cultured with S100A4-overexpressing MH-S cells, proliferation activity was significantly enhanced, the apoptosis rate was significantly decreased, and the proportion in G2/M phase was increased, the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, as well as S100A4 expression in MH-S cells, were significantly increased. The expression of α-SMA was also increased. lncRNA MEG3 and α-SMA mRNA levels were significantly elevated, while miR-147 was significantly decreased. Both TGF-β1 and TNF-α levels were significantly increased (all <0.05) . S100A4 overexpression in macrophages upregulates LncRNA MEG3, which may act as a sponge for miR-147, leading to increased p-JAK2/JAK2 and p-STAT3/STAT3 ratios as well as elevated release of TGF-β1 and TNF-α. This activates the pulmonary inflammatory microenvironment and promotes lung fibroblast proliferation, thereby inducing pulmonary fibrosis. - Source: PubMed
Li X JShi M RCai JZong W HZheng D - To investigate the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in aluminum-induced synaptic function impairment. In March 2024, twenty-four SPF-grade C57BL/6J mice were randomly divided into four groups using the random number table method: the control group (normal saline) and the low, medium, and high-dose aluminium exposure groups [20, 40, and 80 μmol/kg aluminum maltol]. The exposure period lasted for 3 months. After treatment, the Morris water maze test was performed to evaluate the effects of aluminum maltol on learning and memory ability of mice. The expression levels of JAK2/STAT3 pathway proteins, postsynaptic density protein 95 (PSD95), and synapsinⅠ (SYNⅠ) were detected by Western blotting. HT22 mouse hippocampal neuronal cells were used for in vitro experiments, which were divided into the aluminum exposure group [control group (blank group), low, medium, and high-dose groups (60, 120, and 240 μmol/L aluminum maltol) ] and the intervention group[control group (blank group), Colivelin (JAK2/STAT3 pathway activator) group, aluminum maltol group (120 μmol/L), and Colivelin+aluminum maltol group]. Cell viability was tested using CCK-8, morphological changes were observed under an inverted microscope, and the expression levels of JAK2 and STAT3 genes were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression levels of JAK2/STAT3 pathway proteins, PSD95, and SYN Ⅰ were detected by Western blotting, and the fluorescence intensity of PSD95 and SYN Ⅰ proteins was detected by immunofluorescence staining. One-way analysis of variance was used for inter-group difference analysis, and LSD- test was used for pairwise comparison if the variances were homogeneous, otherwise, Dunnett's T3 test was adopted. The Morris water maze test showed that on the 4th and 5th days of the place navigation trial, the escape latency of mice in the medium and high-dose groups were significantly prolonged compared with the control group (<0.05). In the spatial probe trial, the number of platform crossings and the time spent in the target quadrant were significantly reduced in the medium and high-dose groups compared with the control group (<0.05). Western blotting analysis showed that the protein expression levels of JAK2, phosphorylated JAK2, STAT3, phosphorylated STAT3, PSD95, and SYN Ⅰ in the hippocampus were significantly decreased in the medium and high-dose groups compared with the control group (<0.05). Compared with the control group, the cell viability of HT22 cells in the medium and high-dose groups were decreased (<0.05) ; compared with the control group and the low-dose group, the number and length of the synaptic connections in the medium and high-dose groups were reduced (<0.05) ; compared with the control group and the low-dose group, the mRNA expression levels of JAK2 and STAT3 and the protein expression levels of JAK2, phosphorylated JAK2, and SYNⅠ in the medium and high-dose groups were all decreased (<0.05) ; the differences in the protein expression levels of STAT3, phosphorylated STAT3, and PSD95 in each dose group were statistically significant (<0.05) ; compared with the control group, the fluorescence intensities of PSD95 and SYN Ⅰ proteins in the medium and high-dose groups were decreased (<0.05). In addition, compared with the aluminum maltol group, the number of synaptic connections between HT22 cells in the Colivelin+aluminum maltol group increased and the length of the connections became longer (<0.05) ; compared with the aluminum maltol group, the expression of JAK2 mRNA in the Colivelin+aluminum maltol group was increased (<0.05), and the expressions of JAK2, phosphorylated JAK2, phosphorylated STAT3, PSD95 and SYNⅠ proteins were all increased (<0.05), and the fluorescence intensities of PSD95 and SYN Ⅰ proteins were also increased (<0.05) . Aluminium maltol can lead to synaptic function impairment, and the JAK2/STAT3 signaling pathway may be involved in the related regulation. - Source: PubMed
Lei M MXiao W JXu XNiu QYang X J