SU6656 / Pfizer, Hokkaido University - LARVOL DELTA

The regulation of organic anion transporting polypeptide 1B1 by nonreceptor tyrosine kinase YES1. (PubMed, Drug Metab Dispos) - "In this study, OATP1B1 uptake function was found to be significantly suppressed by SRC proto-oncogene, non-receptor tyrosine kinase family kinase inhibitors, with SU6656 demonstrating the most potent inhibitory effect...Abrogation of Caveolin-1 exhibited no effect on the interaction between YES-1 and OATP1B1 but reduced the phosphorylation level of the transporter. Taken together, inhibitors of YES-1 may alter the uptake function of OATP1B1, potentially leading to drug-drug interactions related to post-translational modification."

Journal • Oncology • CAV1 • SRC

Mesenchymal stem cells improve ovarian function by suppressing fibrosis through CTGF/FAK signalling in systemic lupus erythematosus. (PubMed, Lupus Sci Med) - "This study demonstrated that UC-MSC treatment ameliorated ovarian dysfunction and attenuated ovarian fibrosis in lupus mice by modulating the CTGF/FAK-Tyr576/577 phosphorylation pathway."

Journal • Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Transplantation • CD4 • CTGF • ER • IL1B • TNFA

Advanced age and female sex protect cerebral arteries from mitochondrial depolarization and apoptosis during acute oxidative stress. (PubMed, Aging Cell) - "Inhibiting TRPV4 channels with HC-067047 (1 μM) or Src kinases with SU6656 (10 μM) reduced Ca2+ entry and SMC death to H2 O2 most effectively in PCAs from young males...We conclude that in males, chronic oxidative stress during aging increases the resilience of cerebral arteries, which contrasts with inherent protection in females. Findings implicate TRP channels and Src kinases as targets to limit vascular damage to acute oxidative injury."

Journal • Metastases • CNS Disorders • Vascular Neurology

Amphipathic Helical Peptide L37-pA Protects Against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor. (PubMed, Am J Respir Cell Mol Biol) - "Src inhibitor SU6656 attenuated KOdiaPC- induced EC permeability and inflammation, but inhibition of toll-like receptors TLR1, TLR2, TLR4, and TLR6 had no such protective effects. CD36 knockout mice were more resistant to Tr-OxPLs-induced lung injury and L37pA was equally effective in ameliorating Tr-OxPL-induced vascular leak and lung inflammation in mice as determined by Evans blue extravasation assay and total cells and protein content in BAL. Altogether, these results demonstrate an essential role of CD36 in mediating Tr-OxPL-induced EC dysfunction and suggest a strong therapeutic potential of CD36 inhibitory peptides in mitigating lung injury and inflammation."

IO biomarker • Journal • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases • CD36 • CDH5 • TLR2 • TLR4

Ligand-independent activation of platelet-derived growth factor receptor β promotes vitreous-induced contraction of retinal pigment epithelial cells. (PubMed, BMC Ophthalmol) - "The data shown here will improve our understanding of the mechanism by which PDGFRβ can be activated by non-PDGFs in the vitreous via an intracellular route of ROS/SFKs and provide a conceptual foundation for preventing PVR by inhibiting PDGFRβ transactivation (ligand-independent activation)."

Journal • Retinal Disorders • PDGFRA • PDGFRB

Kaempferol suppresses glioma progression and synergistically enhances the antitumor activity of gefitinib by inhibiting the EGFR/SRC/STAT3 signaling pathway. (PubMed, Drug Dev Res) - "Similarly, Kae further enhanced the inhibition of p-SRC caused by SU6656. Kae played a potential role and synergistic antiglioma effects with Gef by inhibiting the phosphorylation of EGFR/SRC dual targets. Kae is expected to be a candidate drug or chemosensitizer in glioma therapy."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • SRC

Neuroendocrine mechanisms in oxaliplatin-induced hyperalgesic priming. (PubMed, Pain) - "Inhibitors of second messengers involved in the maintenance of Type I (cordycepin) and Type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN."

Journal • Infectious Disease • Oncology • Pain • Peripheral Neuropathic Pain • Respiratory Diseases • PRKCE

Inhibition of Oncogenic Src Ameliorates Silica-Induced Pulmonary Fibrosis via PI3K/AKT Pathway. (PubMed, Int J Mol Sci) - "LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • CSK • TGFB1

Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function. (PubMed, Biomed Res Int) - "To explore the effects of Fyn, HTR-8/SVneo and JEG-3 cells were transfected with Fyn shRNA or overexpression plasmid or treated with the Fyn activity inhibitor SU6656 or ERK1/2 inhibitor U0126...Our study first detected the expression of Fyn in trophoblast cells. Fyn played pivotal roles in trophoblast cell behaviors and function, ERK1/2 was one of its targets, and MMP2/9 and STAT3 may also be involved in the regulatory mechanism."

Journal • FYN • IFNG • IL4 • MMP2 • MMP9 • STAT3 • TGFB1 • TNFA

Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib. (PubMed, Head Neck) - "The results demonstrate potential benefit of SFK inhibition in HNSCC but they also highlight challenges due to non-specificities of the different drugs."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Dysregulated Erythroid Mg Efflux in Type 2 Diabetes. (PubMed, Front Cell Dev Biol) - "In contrast, incubation with selective Src family kinase inhibitors PP2 or SU6656 reduced glucose-stimulated exchange activation (p < 0.01)...These data suggest that the reduced RBC Mg content of T2D RBC reflects enhanced RBC Na/Mg exchange subject to regulation by Src family kinases and by the N-glycosylation state of one or more membrane proteins. The data extend our understanding of dysregulated RBC Mg homeostasis in T2D."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Fyn and argonaute 2 participate in maternal-mRNA degradation during mouse oocyte maturation. (PubMed, Cell Cycle) - "Our aim was to examine the role of Fyn and AGO2 in degradation of maternal-mRNAs during oocyte maturation by either suppressing their activity with SU6656 - an SFKs inhibitor; or by microinjecting DN-Fyn RNA for suppression of Fyn and BCl-137 for suppression of AGO2...Inhibition of AGO2 prevented the degreadation of at least five maternal-mRNAs, whereas inhibition of Fyn/SFK prevented degradation of at least five Fyn maternal-mRNAs and two SFKs maternal-mRNAs; pointing at their role in promoting the physiological degradation which occurs during in-vivo oocyte maturation. Our findings imply the involvement of Fyn/SFKs in stabilization of maternal-mRNA at the GV stage and the involvement of Fyn, SFKs and AGO2 in degradation of maternal mRNAs during oocyte maturation."

Journal • Preclinical • Solid Tumor • AGO2

Angiotensin (ang) 1-7 inhibits ang II-induced atrial fibrosis through regulating the interaction of proto-oncogene tyrosine-protein kinase Src (c-Src) and Src homology region 2 domain-containing phosphatase-1 (SHP-1)). (PubMed, Bioengineered) - "Ang II-induced HL-1 cell model and a rat model of Ang II-induced atrial remodeling were constructed and intervened with Ang II Ang-(1-7), AngII +Ang-(1-7), Ang II+ c-Src specific inhibitor (SU6656), and Ang II + Ang-(1-7) + SSG (SHP-1/2 specific inhibitor, stibogluconate), respectively...Ang-(1-7) could reverse the changes related to Ang II-induced atrial fibrosis in rats. In conclusion, Ang-(1-7) antagonized Ang II-induced atrial remodeling by regulating SHP-1 and c-Src, thereby affecting the MAPKs/Akt signaling pathway."

Journal • Fibrosis • Immunology • Oncology • CTGF • MMP2 • TGFB1 • TIMP1

PCB and TCDD derived embryonic cardiac defects result from a novel AhR pathway. (PubMed, Aquat Toxicol) - "Atlantic sturgeon hearts show parallels to contaminant exposed zebrafish cardiac phenotype at the tissue level. These data suggest that the mechanism for PCB and TCDD action in the heart is, in part, distinct from the canonical mechanism described in the literature and that cardiac defects are impacted by this nongenomic mechanism."

Journal • CDH5

Src-mediated Tyr353 phosphorylation of IP3R1 promotes its stability and causes apoptosis in palmitic acid-treated hepatocytes. (PubMed, Exp Cell Res) - " PA promotes the Tyr353 phosphorylation of IP3R1 by activating the src pathway and increasing the protein stability of IP3R1, which consequently results in mitochondrial Ca overload and mitochondrial dysfunction in hepatic cells. Our results also suggested that inhibition of the src/IP3R1 pathway, such as by SU6656, may be a novel potential therapeutic approach for the treatment of NAFLD."

Journal • Hepatology • Liver Failure • Metabolic Disorders • Non-alcoholic Fatty Liver Disease

Up-regulated fibronectin in 3D culture facilitates spreading of triple negative breast cancer cells on 2D through integrin β-5 and Src. (PubMed, Sci Rep) - "In addition, the levels of phosphorylated Src were found to be increased in 3D and the treatment of cells with SU6656, an inhibitor of Src, decreased the rate of cell spreading on FN. Collectively, these studies demonstrate that increased cellular FN in 3D suspension culture facilitates cancer cell attachment and spreading via integrin β-5 and Src, suggesting that the increased FN promotes initial attachment of cancer cells to secondary organs after circulation during metastasis."

Journal • Preclinical • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Src activation in the hypothalamic arcuate nucleus may play an important role in pain hypersensitivity. (PubMed, Sci Rep) - "Neither the Src knockdown nor the systemic application of SU6656 affected the mechanical and thermal sensitivity of the normal rats. Thus, Src activation in the ARC may be a key event for formation and maintenance of pain hypersensitivity associated with peripheral inflammation."

Journal • Immunology • Inflammation • Pain