TG-101348 Mechanisms: JAK2 inhibitor
- Known as:
- TG-101348 Mechanisms: JAK2 suppressor
- Catalog number:
- A-1140
- Product Quantity:
- 5mg
- Category:
- -
- Supplier:
- Activ
- Gene target:
- TG-101348 Mechanisms: JAK2 inhibitor
Related genes to: TG-101348 Mechanisms: 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: TG-101348 Mechanisms: JAK2 inhibitor
Related articles to: TG-101348 Mechanisms: JAK2 inhibitor
- Diabetic muscle infarction (DMI) is an uncommon and frequently underrecognized microvascular complication of longstanding diabetes mellitus characterized by spontaneous ischemic necrosis of skeletal muscle. Polycythemia vera (PV) associated with JAK2 exon 12 mutations represents a rare subtype of myeloproliferative neoplasm that typically presents with isolated erythrocytosis and suppressed serum erythropoietin levels. The coexistence of these two uncommon disorders is exceptionally rare and may create significant diagnostic challenges because painful limb swelling can mimic thrombotic, infectious, inflammatory, or neoplastic conditions. We report the case of a 52-year-old man with poorly controlled type 2 diabetes mellitus who presented with a 3-week history of progressive atraumatic pain and swelling of the left thigh. Doppler ultrasonography excluded deep vein thrombosis and abscess formation, while magnetic resonance imaging demonstrated diffuse muscle edema, short tau inversion recovery (STIR) hyperintensity, and characteristic findings consistent with DMI. Laboratory investigations revealed marked erythrocytosis (hemoglobin 19.9 g/dL), thrombocytosis, and suppressed serum erythropoietin levels. Bone marrow examination demonstrated hypercellularity with erythroid predominance, and molecular testing identified a JAK2 exon 12 mutation, fulfilling contemporary diagnostic criteria for polycythemia vera. Conservative management of DMI together with therapeutic phlebotomy for PV resulted in progressive clinical improvement. This case highlights the importance of maintaining a broad differential diagnosis when evaluating painful limb swelling in patients with diabetes mellitus and persistent erythrocytosis. Recognition of coexisting disorders through careful integration of clinical assessment, imaging, and hematological investigation allows timely diagnosis, avoids unnecessary invasive procedures, and facilitates appropriate disease-specific management. - Source: PubMed
Publication date: 2026/09/05
Rodrigues Isabel VSitari CostantinBlanco Saez RosárioSantos JoaoNogueira PaulaPimenta de Castro Ana - - Source: PubMed
Publication date: 2026/10/05
Bi JianSun KangWu HaoChen XiuliTang HaiyingMao Jingwei - Receptor tyrosine kinases are critical regulators of cell survival, mediating responses to environmental changes and maintaining biological responsiveness. However, despite growing interest in developing senolytics that target survival factors in senescent cells as a promising strategy to overcome age-related diseases, the therapeutic potential of RTKs in senescence remains largely unexplored. In this study, we aimed to identify senolytic compounds that modulate RTK signaling and ameliorate age-related phenotypes by selectively inducing senescent cell death. Using a drug screening approach, we identified sunitinib, a multi-targeted RTK inhibitor that effectively suppresses PDGFR activation and induces apoptosis specifically in senescent HDFs (sHDFs) by activating caspase-9, -3, and -7. Moreover, in a mouse model of bleomycin-induced lung fibrosis in which senescent cells accumulate in the tissue, sunitinib reduced senescent cells and suppressed SASP expression. These findings, together with the observed increase in PDGFRβ phosphorylation in aged cells, led us to hypothesize that modulating PDGFRβ activity could induce senolysis. Indeed, knockdown of PDGFRβ expression sensitized senescent cells to cell death, with minimal effects on non-senescent HDFs (nsHDFs). At the mechanistic level, PDGFRβ and its downstream pathways, including the JAK2-STAT3 pathway, contributed to the senolytic response to sunitinib. Notably, sunitinib-induced JAK1 phosphorylation contributed to resistance to sunitinib in nsHDFs. Our findings suggest that sunitinib is a promising senolytic agent and that targeting PDGFRβ may represent a previously unknown approach to senolytics. Therefore, our study may provide a potential therapeutic strategy for age-related diseases associated with chronic inflammation. - Source: PubMed
Publication date: 2026/10/05
Cho Hyun-JiRyu Sung JinKim Byung JuHwang Jeong-AYun AhyeonKim Eok-CheonKim Jae-RyongPark Tae JunLee Sung BaeKim Young ZoonLee Yun-IlPark Sang ChulLee Young-Sam - Myeloproliferative neoplasms (MPNs) are clonal hematopoietic neoplasms characterized by a substantial risk of arterial and venous thrombosis, which remains a major cause of disease-related morbidity and mortality. Beyond abnormalities in blood-cell counts and rheology, MPN-associated thrombosis is increasingly recognized as a consequence of chronic thromboinflammation arising from dysregulated interactions among leukocytes, platelets, endothelial cells, inflammatory mediators, and the coagulation system. The canonical driver mutations JAK2, CALR, and MPL converge on constitutive JAK-STAT signaling but are associated with differential thrombotic risk, with JAK2V617F being most consistently linked to an increased risk of thrombosis. Growing evidence suggests that thrombotic complications in MPNs are not solely attributable to clonal expansion and quantitative hematologic abnormalities but also involve qualitative alterations in immune-cell function, platelet activation, endothelial dysfunction, inflammatory signaling, and coagulation. This review summarizes the current mechanistic and clinical evidence linking MPN driver mutations and thromboinflammatory processes to thrombosis and discusses the effects of disease-directed therapies on these interconnected pathways. - Source: PubMed
Publication date: 2026/09/23
Zhang HanluXiong HaoGuo XuegeWang XiaoLi LijuanZhang Liansheng - Sepsis-induced cardiomyopathy (SICM) contributes greatly to high mortality in critically ill patients. Accumulating evidence indicates that miRNAs play key roles in sepsis-related organ injury. This work investigated the function and molecular mechanism of miR-454-3p in SICM, along with its potential clinical utility. A total of 100 healthy controls and 210 sepsis patients were enrolled. Sepsis patients were categorized into non-cardiomyopathy group (non-CM, n=105) and SICM group (n=105). Receiver operating characteristic (ROC) curve analysis, multivariate logistic regression, and Cox regression were performed to assess the clinical value of miR-454-3p. In vitro functional experiments were conducted using LPS-stimulated AC16 cardiomyocytes. The dual-luciferase reporter assay verified the targeting relationship between miR-454-3p and STAT3. miR-454-3p expression decreased progressively from healthy controls to non-CM patients and further to SICM patients. miR-454-3p demonstrated good diagnostic performance for SICM. Multivariate analysis identified miR-454-3p as both an independent protective factor against SICM and an independent predictor of favorable prognosis. Cellular experiments revealed that miR-454-3p directly binds to the 3'UTR of STAT3 and suppresses STAT3 expression. Functional assays indicated that miR-454-3p attenuates LPS-induced cardiomyocyte apoptosis, inflammation, and oxidative stress, whereas STAT3 overexpression reverses these protective phenotypes. Furthermore, western blot analysis showed that miR-454-3p inhibits activation of the JAK2/STAT3/NF-κB inflammatory cascade. In vitro assays suggest that miR-454-3p alleviates LPS-triggered cardiomyocyte damage by negatively regulating STAT3 and suppressing the JAK2/STAT3/NF-κB inflammatory cascade. Our single-center observational data indicate that circulating miR-454-3p correlates independently with SICM incidence and 28-day all-cause mortality, implying its potential value as a candidate diagnostic and prognostic biomarker for SICM. Nevertheless, correlational findings from this cross-sectional cohort cannot confirm causal relationships, and large-scale multicenter prospective cohorts are needed for external validation to verify its clinical utility. - Source: PubMed
Publication date: 2026/10/03
Sha ZimoHou TianzhichaoZhou TaojieBao YangyangWei YueLing TianyouWu Liqun