Burger's Medicinal Chemistry and Drug Discovery, by Donald J. Abraham

By Donald J. Abraham

This is often quantity five: Chemotherapeutic brokers, of Burger's Medicinal Chemistry and Drug Discovery, sixth variation. This new quantity comprises serious new chapters on Molecular Biology of melanoma, man made Anti-angiogenic brokers and Selective Toxicities.

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A suggested model for HNPCC development starts with a mutation in the MMR genes followed by another mutation in a gene such as APC. These two events lead to cellular hyperproliferation. Next, a mutation occurs leading to the inactivation of the wild-type allele of the MMR gene. Because of this MMR defect, mutations in other genes involved in tumor progression, such as deleted in colon cancer (DCC), p53, and K-ras, occur. A variety of genes are responsible for the different inherited forms of GI cancers.

10). When unphosphorylated, RB binds to the E2F transcription factor and prevents transcriptional activation of E2F target genes. This normally occurs during the M and early G1 phases of the cell cycle. During late GI, S, and G2 phases, RB is phosphorylated. When phosphorylated, RB can no longer bind to E2F. This release from inhibition allows E2F to activate transcription of S-phase genes and the cell cycle progresses. When loss of RB function occurs because of various mutations in the Rb gene, the cell cycle becomes deregulated, and uncontrolled cell division results.

P53 that is unable to enter the nucleus cannot induce the exvression of downstream effector genes that are necessary for mounting the cellular response to genotoxic stress. Activation of p53 by ionizing radiation (IR) and other DNA damaging agents involves a complex set of interdependent post-translational modifications that control protein1 protein associations, protein turnover, and subcellular localization. Under normal conditions, levels of p53 are kept minimal by ubiquitination and proteosome-mediated degradation that contributes to the short half-life (3-20 min) of the protein.

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Burger's Medicinal Chemistry and Drug Discovery, by Donald J. Abraham
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