Abstract: The present disclosure provides compounds and methods for inhibiting DNA-dependent protein kinase (DNA-PK). Aspects of the present disclosure also include methods of using the compounds to treat diseases, including, but not limited to, cancer. In certain embodiments, the compounds inhibit DNA-PK and thus sensitize cancers to therapies such as chemotherapy and radiotherapy. Certain compounds of the present disclosure are in the form of prodrugs that release the DNA-PK inhibitor in hypoxic tissue such as is known to occur in cancers. Aspects of the present disclosure also include methods of using the compounds for repairing a DNA break in a target genomic region or for modifying expression of one or more genes or proteins. Compounds provided are of formula.

Abstract: The present disclosure provides compounds and methods for inhibiting DNA-dependent protein kinase (DNA-PK). Aspects of the present disclosure also include methods of using the compounds to treat diseases, including, but not limited to, cancer. In certain embodiments, the compounds inhibit DNA-PK and thus sensitize cancers to therapies such as chemotherapy and radiotherapy. Certain compounds of the present disclosure are in the form of prodrugs that release the DNA-PK inhibitor in hypoxic tissue such as is known to occur in cancers. Aspects of the present disclosure also include methods of using the compounds for repairing a DNA break in a target genomic region or for modifying expression of one or more genes or proteins.

Abstract: The failure of many anticancer drugs to control growth of solid cancers may stem in part from inadequate delivery to tumor regions distant from vasculature. However, extricating the effect of tissue penetration from the many other factors that affect a drug's efficacy in tumors with distance from vasculature is generally not possible. The present invention relates to an effect-based assay which employs a multilayered cell culture (MCC), a tissue-engineered disc grown from tumor cells on a permeable membrane. One side of the culture may be exposed to a drug or other test substance while the other side is temporarily sealed off. Cells adjacent both the exposed side and the sealed side, of the MCC may then be compared since they have similar rates of proliferation and other biochemical properties. For example, the effect of the drug or other the test substance may be evaluated by immunohistochemical or other labeling techniques.

Abstract: Method and apparatus for growing cell cultures consisting of a plurality of layers includes a chamber for submerging cells in a medium while supporting and binding them to a semi-permeable membrane. A stirrer is positioned within the chamber and continuously stirs the medium to constantly circulate it past the exposed surface of a semi-permeable membrane on one side of the cell culture and along the exposed surface of the cell culture growing on the membrane and remote from the membrane to transfer nutrients to both surfaces of the cell either directly or through the membrane without disrupting the cell culture on the membrane.