Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 8, Issue 7, 2008

Calcium is a ubiquitous second messenger and is involved in virtually all cellular functions. Cellular events being regulated by calcium include gene transcription, metabolism, proliferation and apoptosis. Cancer growth is based on increased proliferation, decreased differentiation and decreased apoptosis. Therefore, the intracellular Ca2+-homeostasis has become one of the focuses in current cancer research. Elevation of the cy Read More

Ribosomal S6 kinase (RSK) is a family of serine/threonine kinases that has been identified as a promising anti-cancer target. While a number of protein kinase inhibitors that have potent activity against other serine/threonine kinases were shown to also inactivate RSK, there is keen interest in the three different inhibitor chemotypes that were shown to be RSK specific, since these compounds have tremendous utility as chemic Read More

Proteins with tyrosine kinase activity are recognized as key regulators of cellular processes including growth and differentiation. Tyrosine kinase receptors e.g. EGFR and soluble tyrosine kinase proteins e.g. JAK-2, have emerged as essentials in cell survival for cervical carcinoma and acute myeloblastic leukemia, respectively. These receptors and soluble cytoplasm networks have been studied in detail and finally pharmacolo Read More

Cyclins and CDKs play critical roles in DNA synthesis and cell division. Alterations in their function may lead to the disruption of normal cell growth and apoptosis, and subsequently, result in carcinogenesis. Elevated levels of cyclins and CDKs are frequently observed in a wide range of different types of human cancers. Understanding of molecular mechanisms underlying the cell cycle effects in response to the chemotherapeutic Read More

The steroid sulfatase (STS) enzyme plays a pivotal role in the formation of biologically active steroid hormones. Its involvement in the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone, respectively, is an important step in the formation of estradiol and androstenediol, both of which are estrogenic steroids that can stimulate tumor growth. Consequently, as STS is widely distr Read More

The sulfonamides constitute an important class of drugs, which display a variety of activities including antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic and antithyroid effectiveness. A number of sulfonamides have been reported to be potent anticancer agents, which interact with a wide range of different cellular targets. Among these interesting sulfonamides, the diaryl or heterocyclic sulfonamides have recen Read More

Lamellarins are a large family of marine alkaloids with potential anticancer activity that have been isolated from diverse marine organisms, mainly ascidians and sponges. All lamellarins feature a 3,4-diarylpyrrole system. Pentacyclic lamellarins, whose polyheterocyclic system has a pyrrole core, are the most active compounds. Some of these alkaloids are potently cytotoxic to various tumor cell lines. To date, Lam-D and Lam-H ha Read More

One promising therapeutic strategy for treating cancer is to specifically target signal transduction pathways that have a key role in oncogenic transformation and malignant progression. Hsp90 is an emerging therapeutic target of interest for the treatment of cancer. It is responsible for modulating cellular response to stress by maintaining the function of numerous signalling proteins - known as ‘client proteins’ - that are Read More

Cladribine, i.e.2-deoxy-Chloroadenosine is currently in use as chemotherapeutic agent in chronic lymphoid malignancies and pediatric acute myelogenous leukemia whereas the structurally related counterpart, 2-Chloroadenosine, has been less studied. Nevertheless, 2-Chloroadenosine has been shown to be capable of inducing apoptosis in several cell lines by acting either via adenosine receptors or via uptake that is foll Read More

A solid tumour forms an organ-like structure that is comprised of cancer cells as well as stroma cells (fibroblasts, inflammatory cells) that are embedded in an extracellular matrix and are nourished by vascular network. However, tumoral microenvironment is heterogeneous due to the abnormal vasculature network and high proliferation rate of cancer cells. Because of these features, some regions are starved from oxy Read More

Protein kinase CK2 is a ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. A number of structurally unrelated CK2 inhibitors, tested on a variety of cells derived from tumours, including lymphomas, leukaemias, multiple myeloma and prostate carcinoma, display a proapoptotic effect whic Read More

Numerous proteins responsible for cell proliferation and differentiation exist either as hetero or homodimers or become activated through dimerization as a key step in their respective signaling cascade. Many of these proteins have been identified as major components in oncogenic signaling pathways and have become popular targets for the development of anti-tumor agents. For this reason, bivalent anti-cancer dr Read More