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Download Ebook Matematika Diskrit Dan Aplikasinya Pada Ilmu Komputer
download matematika diskrit dan aplikasinya pada ilmu komputerChemotherapy has become a standard approach for tumor treatment. However, chemotherapy has side effects that are disfiguring and life-threatening. The main problem of using chemotherapy for cancer treatment is the resistance of some cancer cells to drugs. A well-known example is cancer cells that express the efflux transporter ABCG2. Recent studies suggest that molecular targeting of ABCG2 by small molecules could be a promising approach for cancer therapy. For example, the first reported small molecule inhibitor of ABCG2 for cancer treatment was a second generation green tea catechin, gimatecan (Figure 1). Gimatecan inhibits ABCG2-mediated drug resistance and improves the chemotherapy efficacy. However, gimatecan has some issues, including high toxicity, low cell permeability, and low solubility, which hinder further clinical development.
Figure 1: Structure of gimatecan (left). The binding of gimatecan to ABCG2 protein (right). ChemR23 is important for bone marrow development and survival and is overexpressed in inflammatory diseases such as rheumatoid arthritis and in malignancies. Small molecules targeting ChemR23 have been developed but their effect on bone marrow development and function in animal models is unknown.
Omidbakht et al. reported a second generation aryl imidazole derivative that efficiently inhibits ABCG2 in cancer cells. This compound bound to the C-pocket of ABCG2 with high affinity. The author tried to develop new chemosensitizers with the structure of gimatecan, in particular those that were effective in cancers overexpressing ABCG2, by using the C-pocket of ABCG2 as a template and discovered a new chemosensitizer, aryl imidazole derivative 20, which showed potent inhibition of ABCG2 with a low level of toxicity in leukemia cells (Figure 2). A key point of the discovery was a new method to predict binding modes of compounds with membrane proteins. This approach can be applied to more membrane proteins and potential drug targets.
Figure 2: The structure of aryl imidazole derivative 20 (left). The molecular binding model of 20 to ABCG2 based on the binding mode of gimatecan (right). The amino acids are shown in red sticks.Q:
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Maddalena is an unincorporated community in Rhea County, Tennessee. The community is located along the northern terminus of Tennessee State Route 59, a short connector between Tennessee State Route 13 and U.S. Route 64. Despite its name, Maddalena is not to be confused with the nearby settlement of Madison, or Madisonville.
A former settlement, Maddalena is now a cluster of abandoned houses set atop a ridge overlooking the Cumberland River. Maddalena was named after an Italian immigrant who owned land along the creek.
Category:Unincorporated communities in Rhea County, Tennessee
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