BMS-911543 JAK2 inhibitor
- Known as:
- BMS-911543 JAK2 suppressor
- Catalog number:
- a-1175
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- ActivBio Active Biochem
- Gene target:
- BMS-911543 JAK2 inhibitor
Related genes to: BMS-911543 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: BMS-911543 JAK2 inhibitor
Related articles to: BMS-911543 JAK2 inhibitor
- Myelofibrosis is an advanced myeloproliferative neoplasm that is biologically driven by constitutively active JAK-STAT signaling. Resultant effects on hematopoiesis and inflammatory cytokine signaling give rise to an array of clinical manifestations that include proliferative features, splenomegaly, constitutional symptoms, cytopenias, propensity towards leukemic transformation, and risk of thrombosis, with patients exhibiting a high degree of variability in regard to clinical course. This necessitates an individualized treatment approach that accounts for a variety of clinical and therapy-specific factors. JAK inhibitors have emerged as the cornerstone of therapy. With 4 agents now approved in the class, selecting the appropriate agent is of critical importance. In this review we discuss key variables that should be considered in the creation of a therapeutic plan for patients with myelofibrosis. We will review pharmacologic differences between available JAK inhibitors, discuss the patient factors that drive therapy decisions in myelofibrosis, and highlight emerging therapies in the field. - Source: PubMed
Publication date: 2026/07/23
Hunter Anthony MBose Prithviraj - C-C motif chemokine ligand 2 (CCL2) contributes to post-traumatic neuroinflammation and blood-brain barrier (BBB) disruption, but its role in post-traumatic external cerebral herniation and endothelial JAK-STAT signaling remains unclear. - Source: PubMed
Publication date: 2026/08/14
Chen QizuanXia JinbiaoZhang ShangmingPei JiashengLi ZiqiLiu ZhengWei LiangfengWang Shousen - Sepsis-associated encephalopathy (SAE) is a multifactorial medical condition characterized by pronounced neuroinflammation and linked to increased mortality risk and long-term cognitive impairment. Microglial pyroptosis has emerged as a crucial pathogenic mechanism in SAE. CD300f, an immune receptor expressed in microglia, regulates inflammatory processes and neuronal survival, exerting a protective effect against brain injury. However, its specific role in SAE remains unexplored. Bioinformatic analyses revealed upregulated CD300f expression in the hippocampus of SAE mice as well as in the peripheral blood of septic patients. Western blot and qPCR further confirmed increased hippocampal CD300f expression in SAE mice subjected to cecal ligation and puncture (CLP). Knockdown of CD300f promoted Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) phosphorylation, exacerbated microglial pyroptosis, aggravated neuronal damage, and worsened cognitive dysfunction in SAE mice. Conversely, CD300f overexpression attenuated lipopolysaccharide (LPS)- and adenosine triphosphate (ATP)- induced JAK2/STAT3 phosphorylation, suppressed microglial pyroptosis and proinflammatory cytokine release in vitro. Collectively, these loss- and gain-of-function data indicate that the upregulation of CD300f during sepsis represents a compensatory protective response aimed at counteracting hyperactive JAK2/STAT3 signaling and limiting pyroptotic damage. Pharmacological inhibition of STAT3 with Stattic or JAK2 with AG490 similarly inhibited STAT3 phosphorylation and attenuated microglial pyroptosis in vitro. In summary, we demonstrate that CD300f negatively regulates JAK2/STAT3 phosphorylation, attenuates microglial pyroptosis, and alleviates cognitive dysfunction in SAE mice. These findings highlight an association between CD300f and neuroprotection in SAE and suggest its potential as a therapeutic target, warranting further investigation through in vivo gain-of-function studies. - Source: PubMed
Publication date: 2026/08/14
Chen XueSun YeJiang SainanCheng JianiLi HaoyiYin ShengmingXiao Zhaoyang - Janus kinases (JAKs) are central mediators of cytokine-driven signal transducer and activator of transcription (STAT) signaling, and dysregulation of the JAK-STAT axis is implicated in inflammatory, autoimmune, and neoplastic diseases. To identify new small-molecule inhibitors of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), we implemented an integrated virtual screening workflow combining structure-based docking and ligand-based prioritization using the InterBioScreen (IBS) compound library. A drug-likeness filter reduced 521,627 IBS molecules to 116,064 candidates, which were then docked into the ATP-binding sites of JAK1 (PDB ID: 4EI4) and JAK2 (PDB ID: 6VGL) using Glide SP; compounds were prioritized using docking score thresholds of <- 8.5 kcal/mol (JAK1) and <- 9.0 kcal/mol (JAK2), yielding 407 JAK1- and 298 JAK2-focused hits. Subsequent analysis shortlisted 42 candidates for enzymatic evaluation. kinase assays identified multiple nanomolar inhibitors, including compound (IC = 0.032 μM) among the most potent for JAK1 and compound (IC = 0.026 μM) for JAK2. Finally, 100 ns molecular dynamics (MD) simulations supported stable binding for representative complexes, with persistent hinge-region interactions for compound in JAK1 (e.g., Glu957/Leu959) and compound in JAK2 (e.g., Glu930/Leu932), consistent with a stable interaction network in the active site. Collectively, these results define validated IBS-derived hit scaffolds for further optimization and selectivity profiling toward JAK-targeted therapeutics. - Source: PubMed
Publication date: 2026/07/25
Avci AhmetTaşci HayrünnisaSağlık Özkan Begüm NurpelinTozkoparan BirsenKelekçi Nesrin Gökhan - Chronic psychosocial stress is a major driver of depression, yet the glycometabolic mechanisms linking stress exposure to neuroinflammation and synaptic dysfunction remain poorly understood. Here, using a chronic social defeat stress (CSDS) model, we demonstrated that L-fucose supplementation markedly attenuated depressive-like behaviors and suppressed neuroinflammation in the hippocampus. L-fucose also reduced Iba1-positive microglial accumulation, inhibited JAK2/STAT3 inflammatory signaling, and restored the stress-induced loss of synaptic proteins, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits and postsynaptic density protein 95 (PSD95). Mechanistically, CSDS downregulated hippocampal guanosine 5'-diphosphate (GDP)-fucose levels, thereby impairing core fucosylation. This defect was associated with downregulation of key enzymes in the GDP-fucose salvage biosynthetic pathway, including fucokinase (FUK) and fucose-1-phosphate guanylyltransferase (FPGT), both of which were restored by L-fucose administration. Consistently, pharmacological inhibition of fucosylation with 2-fluorofucose (2FF) suppressed GDP-fucose and expression, thereby exacerbating depressive-like behaviors and neuroinflammation in the CSDS model. Furthermore, L-fucose or MF30 alleviated CSDS-induced inflammatory responses in distal colon tissues. Taken together, this study clearly identifies a link between GDP-fucose synthesis and chronic stress and, for the first time, shows that alterations in key enzymes in the GDP-fucose salvage pathway play critical roles in CSDS-induced depressive-like behaviors and neuroinflammation, suggesting that restoring GDP-fucose biosynthetic activation may offer a promising therapeutic strategy for stress-related neuropsychiatric disorders. - Source: PubMed
Publication date: 2026/07/30
Zheng MengFukuda TomohikoZhang SimingWang YueSaito TsukushiZhou YuhangXia BoyuMochizuki KazukiAizawa TerukiIsaji TomoyaGu Jianguo