sirolimus and borrelidin

Mutasynthesis couples the power of chemical synthesis with molecular biology to generate derivatives of medicinally valuable, natural products. Recently, this technique has been exploited by Cambridge-based biotech company Biotica Technology Ltd, and their collaborators, to generate promising new variants of the polyketide anti-cancer compounds rapamycin and borrelidin.

Topics: Chemistry; Drug Design; Fatty Alcohols; Genetic Engineering; Mutation; Sirolimus; Technology, Pharmaceutical

Further progress in the therapy of malignant diseases is expected from the introduction of potent antimetastatic drugs. Surveying of the complex and multi-step behavior of the metastatic process, compounds showing inhibitory action against tumor cell migration may be ranked among the promising antimetastatic agents. Our present study indicate, however, that the antimigratory actions of certain antitumor drugs (doxorubicin, taxol), and inhibitors of signal transduction (PD-98059, LY-294002, SB-203580) are highly dependent on the assay applied (Boyden-chamber, 3D ECM cell culture). It has been proposed that agents interrupting cell-extracellular matrix contacts (hexyldeoxyuridine, borrelidin) and others interfering with the regulatory mechanism of gene translation (rapamycin, ribavirin) could be regarded as leading compounds in the antimetastatic drug development process. Nevertheless, for introducing diagnostically based targeted therapy the forthcoming tasks must include the further elucidation of the molecular mechanisms implicated in the amoeboid and cluster type of cell migration.

Topics: Animals; Antineoplastic Agents; Cell Movement; Chromones; Deoxyuridine; Doxorubicin; Enzyme Inhibitors; Fatty Alcohols; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; Imidazoles; Morpholines; Neoplasm Metastasis; Paclitaxel; Pyridines; Ribavirin; Signal Transduction; Sirolimus