Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 7, Issue 6, 2007

Protein tyrosine kinases (PTKs) play important roles in biochemical signaling events related to cellular activation, differentiation, proliferation, and survival. Because of their contribution to chemotherapy resistance as well as growth of human cancers, several PTKs have emerged as new molecular targets in cancer therapy. The reported clinical successes with the anti- HER2 monoclonal antibody Herceptin in breast cancer Read More

Deregulated activation of protein tyrosine kinases (PTKs) is a frequent event underlying malignant transformation in many types of cancer. The formation of oncogenic fusion tyrosine kinases (FTKs) resulting from genomic rearrangements, represents a common mechanism by which kinases escape the strict controls that normally regulate their expression and activation. FTKs are typically composed of an N-terminal dimerisat Read More

Inhibitors of Janus Kinase 3 (JAK3) show potential as a new class of apoptosis-inducing anti-cancer drugs. In addition, JAK3 inhibitors may also be useful as immunosuppressive agents. Rationally designed selective inhibitors of JAK3 such as JANEX-1, that do not inhibit other Janus kinases have recently undergone extensive preclinical testing that revealed a favorable pharmacodynamic profile. Here we discuss the clinical potenti Read More

Targeting Bruton's tyrosine kinase (BTK) with a small molecule inhibitor may be useful in treatment of BTK-expressing malignancies because of the anti-apoptotic function of BTK in cancer cells. Furthermore, BTK inhibitors also exhibit anti-thrombotic properties that may be desirable in the context of the increased risk of thromboembolic complications in cancer patients. This review will focus on the role of BTK in drug resist Read More

Lung cancer is a leading cause of cancer death. Systemic therapies with cytotoxic chemotherapies remain ineffective. Current research efforts in lung cancer have focused on developing novel agents to target cellular pathways that are altered in lung cancer. Protein tyrosine kinases are a family of oncogenes that regulate important cellular processes such as differentiation, proliferation, cell cycle, motility, and apoptosis. In Read More

Cloned in 1992, Jak2 tyrosine kinase has emerged as a critical molecule in mammalian development, physiology, and disease. Here, we will review the early history of Jak2 as it pertains to its role in classical cellular signaling. We also review how specific structural determinants within Jak2 dictate its overall function. Finally, we will review relatively recent literature as it pertains to the role of Jak2 in neoplastic growth as well as the i Read More

The Src family of kinases has nine known members, all of which are nonreceptor tyrosine kinases involved in signal transduction in both normal and cancer cells. Interest in these kinases has increased recently because of the development, initial clinical success, and low toxicity of pharmacologic inhibitors. c-Src is the best-studied member of the Src family and the one most often implicated in cancer progression. c-Src has multipl Read More

Protein tyrosine kinases catalyze the transfer of phosphoryl groups from ATP to amino acids on proteins and play a fundamental role in signal transduction pathways in mammalian cells. In particular, Src and Src-family are non-receptor tyrosine kinases that regulate cell growth, differentiation, migration, adhesion and apoptosis. Src-family members share common features, with well defined domains. The activati Read More

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to the points of cell contact with the extracellular matrix, called focal adhesions. FAK is involved in several cellular processes including invasion, motility, proliferation and apoptosis. In in vivo animal studies, FAK has been shown to contribute to tumor development and malignancy. Furthermore, FAK expression was shown to be elevated in a numb Read More

The disease of cancer has been ranked second after cardiovascular diseases and plant-derived molecules have played an important role for the treatment of cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Recently, epothilones are being emerging as future potential anti-tu Read More