PIM kinase is consequently emerging as a promising target for cancer therapeutics and immunomodulation. kinases are overexpressed in variety of hematological malignancies solid tumors, their inhibition has become strong therapeutic interest. Currently, some pan-PIM inhibitors being developed under different phases clinical trials. Based on the scaffold structures, they can be classified into va...

RAF kinases have a prominent role in cancer. Their mode of activation is complex but critically requires dimerization of their kinase domains. Unexpectedly, several ATP-competitive RAF inhibitors were recently found to promote dimerization and transactivation of RAF kinases in a RAS-dependent manner and, as a result, undesirably stimulate RAS/ERK pathway-mediated cell growth. The mechanism by w...

Quinoline-3-carboxamides are an essential class of drug-like small molecules that known to inhibit the phosphatidylinositol 3-kinase-related kinases (PIKK) family kinases. The quinoline nitrogen is shown bind hinge region kinases, making them competitive inhibitors adenosine triphosphate (ATP). We have previously designed and synthesized quinoline-3-carboxamides as potential ataxia telangiectas...

Gastrointestinal (GI) cancers that include all of the digestive tract organs are generally associated with obesity, lack exercising, smoking, poor diet, and heavy alcohol consumption. Treatment GI typically involves surgery followed by chemotherapy and/or radiation. Unfortunately, intrinsic or acquired resistance to these therapies underscore need for more effective targeted have been proven in...

There is an extensive list of applications for nucleosides, nucleotides, and their analogues that spans from substrates inhibitors in enzymatic research to anticancer antiviral drugs. Nucleoside phosphates are often obtained by chemical phosphorylation reactions, although nucleoside a promising green alternative. In this work two kinases, D. melanogaster deoxynucleoside kinase B. subtilis deoxy...

The efficacy of small-molecule kinase inhibitors has recently changed standard clinical practice for several solid cancers. Glioblastoma is a solid cancer that universally recurs and unrelentingly results in death despite maximal surgery and radiotherapy with concomitant and adjuvant temozolomide. Several clinical studies using kinase inhibitors in glioblastoma have been reported. The present s...

PURPOSE To analyze whether tyrosine kinase inhibitors blocking VEGF receptors (PTK787/ZK222584 [PTK/ZK] and ZK261991 [ZK991]) can inhibit not only hemangiogenesis but also lymphangiogenesis and whether treatment with tyrosine kinase inhibitors after corneal transplantation can improve graft survival. METHODS Inflammatory corneal neovascularization was induced by corneal suture placement. One ...

An elevated neutrophil-to-lymphocyte ratio (NLR) indicates a poor prognosis across multiple cancers, including non-small cell lung cancer (NSCLC) and is associated with cachexia. EGFR tyrosine kinase inhibitors (TKI) are typically brisk responses prolonged PFS benefit. This study evaluates baseline NLR serial values in EGFR-mutated NSCLC patients receiving TKI therapy. Preliminary findings from...

BACKGROUND Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND RESULTS We administered clinically relevant doses of sorafenib, sunitinib...