Abstract: With the subject invention, a method is provided for preparing a filter membrane including the steps of dispersing a liquid which is generally hydrophobic into the pores of a porous membrane, and applying a solution containing lipids onto at least a first surface of the porous membrane containing the liquid. Advantageously, the subject invention allows for filter membranes to be prepared which can be stored for periods of time without degradation in performance. The subject invention may have applicability in various contexts, but is well-suited for preparing filter membranes for permeability screening, particularly Parallel Artificial Membrane Permeability Assay (PAMPA).

Abstract: With the subject invention, a method is provided for preparing a filter membrane including the steps of dispersing a liquid which is generally hydrophobic into the pores of a porous membrane, and applying a solution containing lipids onto at least a first surface of the porous membrane containing the liquid. Advantageously, the subject invention allows for filter membranes to be prepared which can be stored for periods of time without degradation in performance. The subject invention may have applicability in various contexts, but is well-suited for preparing filter membranes for permeability screening, particularly Parallel Artificial Membrane Permeability Assay (PAMPA).

Abstract: With the subject invention, a method is provided for preparing a filter membrane including the steps of dispersing a liquid which is generally hydrophobic into the pores of a porous membrane, and applying a solution containing lipids onto at least a first surface of the porous membrane containing the liquid. Advantageously, the subject invention allows for filter membranes to be prepared which can be stored for periods of time without degradation in performance. The subject invention may have applicability in various contexts, but is well-suited for preparing filter membranes for permeability screening, particularly Parallel Artificial Membrane Permeability Assay (PAMPA).

Abstract: An article is provided herein for use in seeding cells on at least one filter extending across at least one well of an assay device. The article includes an elastomeric body having spaced-apart first and second surfaces, and at least one channel extending between, and through, the first and second surfaces. The channel is formed to sealingly, and detachably, engage an outer surface of the well with the filter being at least partially encompassed by the channel. Advantageously, with the subject invention, a cell monolayer can be formed on the exterior surface of the filter. The assay device may be a multiwell plate, an insert plate, a column, a test tube, or a pipette.

Abstract: An article is provided herein for use in seeding cells on at least one filter extending across at least one well of an assay device. The article includes an elastomeric body having spaced-apart first and second surfaces, and at least one channel extending between, and through the first and second surfaces. The channel is formed to sealingly, and detachably, engage an outer surface of the well with the filter being at least partially encompassed by the channel. Advantageously, with the subject invention, a cell monolayer can be formed on the exterior surface of the filter. The assay device may be a multiwell plate, an insert plate, a column a test tube, or a pipette.

Abstract: The invention pertains to dog P-glycoproteins and related P-glycoproteins which include dog-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the dog P-glycoprotein. The invention further relates to methods of using such dog P-glycoprotein nucleic acids and polypeptides, especially in methods for determining bioavailability of drugs and for screening for inhibitors of dog PGP. Also included are dog PGP inhibitors which inhibit dog PGP activity by inhibiting the expression or function of dog PGP.

Abstract: The invention pertains to cynomologous monkey P-glycoproteins and related P-glycoproteins which include cynomologous-specific amino acids, as well as nucleic acids which encode those polypeptides. The present invention also includes fragments and biologically functional variants of the cynomologous monkey P-glycoprotein. The invention further relates to methods of using such cynomologous monkey P-glycoprotein nucleic acids and polypeptides, especially in methods for determining bioavailability of drugs and for screening for inhibitors of cynomologous PGP. Also included are cynomologous PGP inhibitors which inhibit cynomologous PGP activity by inhibiting the expression or function of cynomologous PGP.

Abstract: Novel fluorescent substrates of human cytochrome P450 enzymes are provided. Also provided are methods for their manufacture and use. These substrates are useful in assessing cytochrome P450 enzyme activity and in selecting compounds which inhibit cytochrome P450 enzyme activity and, in particular, for identifying potential adverse drug interactions which are mediated by inhibition of cytochrome P450 enzyme activity.

Abstract: Novel fluorescent substrates of human cytochrome P450 enzymes are provided. Also provided are methods for their manufacture and use. These substrates are useful in assessing cytochrome P450 enzyme activity and in selecting compounds which inhibit cytochrome P450 enzyme activity and, in particular, for identifying potential adverse drug interactions which are mediated by inhibition of cytochrome P450 enzyme activity. The compounds are particularly useful for assessing cytochrome P450 CYP3A enzyme activity.

Abstract: Novel fluorescent substrates of the human P450 enzyme CYP2D6 are provided. Also provided are methods for their manufacture and use. These substrates are useful in assessing CYP2D6 enzyme activity and in selecting compounds which inhibit CYP2D6 enzyme activity and, in particular, for identifying potential adverse drug interactions which are mediated by inhibition of CYP2D6 enzyme activity.

Abstract: The present invention pertains to a line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity). Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. The invention also includes mutation assays using these cells, and other cells with similar characteristics.

Abstract: An immortal human cell line stably expressing a multiplicity of cytochrome P450s is provided. Preferably, the cell line is MCL-5, which stably expresses cytochrome P450 IA1, IA2, IIA3, IIIA4, and IIE1, as well as microsomal epoxide hydrolase. The cell line is useful in mutagenicity, toxicity and metabolism studies.

Abstract: The invention provides methods and products equal in a selection system for determining the presence or absence of a vector in a mammlian cell. The vector of the invention carries and is capable of expressing a gene encoding a protein capable of effecting the conversion of a precursor to an essential amino acid. A mammalian cell line is created with conditions capable of causing the vector to be introduced into the mammalian cell line. Then, the created mammalian cell line is grown in medium containing a precursors to the essential amino acid but not containing the growth-supporting amount of the essential amino acid and those cells capable of growing are selected.

Abstract: A line of human blood cells which have high levels of oxidative activity (such as oxygenase, oxidase, peroxidase, and hydroxylase activity) is disclosed. Such cells grow in suspension culture, and are useful to determine the mutagenicity of xenobiotic substances that are metabolized into toxic or mutagenic substances. Mutation assays using these cells, and other cells with similar characteristics, are also disclosed.