Current Medicinal Chemistry - Volume 10, Issue 9, 2003

The recent use of chemical genomics to identify bioactive small molecules that interact with specific proteins has had a tremendous impact on both the functional analysis of genes and drug development. Accordingly, the current review focuses on the utilization of this new research engine in the target identification and validation of antiangiogenic agents capable of regulating the growth and spread of cancer cells. In addition, the Read More

In this review, I have mainly described the cell cycle inhibitors isolated from microbial metabolites. Once the molecular target of the inhibitor is determined, the inhibitor can be used as bioprobe to dissect the diverse aspect of biological functions in chemical biology research. Reveromycin A and phosmidosine inhibited the protein synthesis of mammalian cells and arrested the cell cycle at G1 phase. Lucilactaene arrested cells Read More

Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for stability and function of multiple mutated, chimeric, and over-expressed signaling proteins that promote cancer cell growth and / or survival. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, HER2 / Neu (ErbB2), and HIF-1α. Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the destabilization and Read More

Recruitment of cytoplasmic signaling proteins into the nucleus is an essential step in the activation of gene expression in response to an extracellular signal. Nucleocytoplasmic transport of macromolecules is mediated by the transport receptors of an importin β family. Post-translational modifications and masking / unmasking of specific signal sequences responsible for nuclear import and export are importa Read More

Cancer is the leading cause of death in United States and World wide. Drug discovery and development for cancer therapeutics takes several years before a patient is benefited from a new drug. The average time length from start to finish is approximately 15 years. This time length includes 4-5 years of basic research, discovery, preclinical development and validation studies. Next, it takes approximately 7-10 years for a drug to Read More

Chemical genomics represents a cooperation of biology and chemistry to identify and intervene the biological targets. Small molecules with diverse structural characteristics should be used to validate the target through interfering with the biological processes. Because of the limitation of existing chemical libraries, the diversity can be exploited using both the molecular design techniques; structure-based design and ligand- Read More

In recent years there has been a growing interest in computer-based screening. One of the driving forces has been the increased efficiency of protein crystallography leading to the real possibility of using structure-based design as a significant contributor to the discovery of novel ligands. In 1957 after 22 years of work the first protein structure, determined by x-ray crystallography was produced [1]. Now the process has bec Read More

Ribonucleases (RNases) have proven to be excellent model systems for the study of protein structure, folding and stability, and enzyme catalysis, resulting in four Nobel Prize lectures in chemistry. Beside this ‘academic’ success, RNases are also relevant from a medical point of view. The RNA population in cells is controlled post-transcriptionally by ribonucleases (RNases) of varying specificity. Other therapeutic proteins like angi Read More

Vacuolar-ATPase (V-ATPase) has been proposed as a drug target in osteoporosis due to its involvement in bone resorption, and as a target in cancer due to potential involvement in tumor invasion and metastasis. The classical selective inhibitors of V-ATPase are microbial macrolides of the bafilomycin and concanamycin class. These inhibitors have proven to be too toxic for therapeutic use, however recent structure-activity Read More