Abstract: Apparatus and method for classifying multi-dimensional biological data are described. In some embodiments, a methodology for deriving a linear classification rule can be used for predicting a biological activity or a biological state. Advantageously, the methodology described herein facilitates obtaining robust and sparse classifiers that account for uncertainty involved in real-world experiments and improve computational efficiency and ease of interpretation of results.

Abstract: An interactive system for facilitating hypothesis construction by correlating and presenting gene expression data, bioassay data, and compound activity data, and associating gene and compound function information with product information, and facilitating product purchase, is disclosed.

Abstract: Compounds of formula 1 modulate the activity of Rho C: wherein R1 is H, lower alkyl, aralkyl, aryl-lower alkenyl, or —(CH2)nCH(R7)NR8R9, where n is 0–6 inclusive, R7 is H, lower alkyl, aryl, or aralkyl, R8 is H, lower alkyl, cyclo-alkyl, aryl, or aralkyl, and R9 is R, RCO—, ROCO—, or RNHCO—, where R is lower alkyl, cycloalkyl, aryl, or aralkyl, wherein aryl and aralkyl are substituted with 0–3 substituents selected from the group consisting of lower alkyl, halo, nitro, —OH, trifluoromethyl, or lower alkoxy; R2 is lower alkyl, aryl, aralkyl, or —(CHR10)m—(CO)—R11, wherein m is 0–4, R10 is H or lower alkyl, and R11 is lower alkyl, cycloalkyl, aryl, or aralkyl, wherein aryl and aralkyl are substituted with 0–3 substituents selected from the group consisting of lower alkyl, halo, nitro, —OH, trifluoromethyl, or lower alkoxy; R3, R4, R5, and R6, are each independently H, lower alkyl, halo, nitro, OH, lower alkoxy, NH2, lower alkylamino, di(lower alkylamino), trifluoromethyl, or SH; or a pharmaceutically acce

Abstract: Compounds of formula 1 modulate the activity of Rho C: wherein R is a direct bond, lower alkylene, —C(O)NH—, or —NHC(O)—; Ar is aryl or heteroaryl, substituted with R7, R8, R9, and R10, wherein R7, R8, and R9 are each independently H, halo, lower alkyl, OH, lower alkoxy, and R10 is H, halo, lower alkyl, OH, lower alkoxy, or forms a ring with R1; R1 is H, lower alkyl, or forms a ring with R10; R2, R3, R4, R5, and R6 are each independently H, lower alkyl, halo, nitro, OH, lower alkoxy, NH2, lower alkylamino, di(lower alkyl)amino, or two adjacent groups together form a saturated or unsaturated ring; or a pharmaceutically acceptable salt thereof.

Abstract: Compounds of formula 1 are effective modulators of PI3 kinase: wherein R1 is H, hydroxy, amino, lower alkyl, or trihalomethyl; R2 is amino, lower alkylamino, lower acylamino, arylamino, arylacyl-amino, heteroaryl-amino, heteroaryl-acyl amino, where aryl and heteroaryl are substituted with 0-3 substituents selected from the group consisting of halo, trihalomethyl, hydroxy, lower alkyl and lower alkoxy, or a substituent of the form —(CH2)n—C(?X)—R8, where n is 014 3 inclusive and X is O or NR9, where R9 is H, lower alkyl, or R1 and R2 together form —CH?N—X— where X is CH, NH, O, or S, and R8 is H, lower alkyl, lower alkoxy, aryl, aralkyl, or —(CH2)mCR10R11R12, where m is 0-3 inclusive, and R10, R11, and R12 are each independently H, lower alkyl, aryl, aralkyl, hydroxy, lower alkoxy, aryloxy, aralkoxy, amino, lower alkyl-amino, arylamino, aralkylamino, heteroaryl amino, or heteroaralkyl amino, where aryl and heteroaryl are substituted with 0-3 substituents selected from the group consisting of halo, hydrox

Abstract: Compounds of formula 1 are effective modulators of PI3 kinase: wherein X is CR9R10, O, NR11 (where R9 and R10 are each independently H, lower alkyl, lower alkoxy, or halo, and R11 is H or lower alkyl); or single bond; R1 is H, lower alkyl, aryl, aralkyl; R2 is H, lower alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, lower alkoxy, amino, lower alkylamino, lower acylamino, arylamino, arylacyl-amino, heteroaryl-amino, heteroaryl-acyl amino, thio, lower alkylthio, arylthio, or aralkyl-thio, where aryl and heteroaryl are substituted with 0-3 substituents selected from the group consisting of halo, trihalomethyl, hydroxy, lower alkyl and lower alkoxy; R3, R4, R5, R6, R7, and R8 are each independently H, lower alkyl, lower alkoxy, or halo; or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds of formula 1 modulate the activity of Rho C: wherein R1 is H, OH, or lower alkyl; R2, R3, R4, R5, and R6 are each independently H, halo, lower alkyl, OH, lower alkoxy, NH2, lower alkylamino, di(lower alkyl)amino, SH, lower alkylthio, NO2, or two residues together form a heterocyclic ring; R7, R8, R9, and R10 are each independently H, lower alkyl, OH, NH2, aryl, or aralkyl, where aryl and aralkyl are substituted with 0-3 moieties selected from the group consisting of halo, OH, NH2, lower alkyl, lower alkoxy, SH, lower alkylthio, and lower alkylamino; R11, R12, R13, R14, R15, and R16 are each independently H, halo, lower alkyl, OH, lower alkoxy, or NO2; or a pharmaceutically acceptable salt thereof.

Abstract: A method for identifying a mutation-sensitive active region of a test protein, by providing a test nucleic acid construct comprising a regulatable promoter polynucleotide and a fusion polynucleotide comprising a test polynucleotide encoding the test protein fused to a reporter gene, wherein said fusion polynucleotide is operably associated with the promoter polynucleotide, wherein expression of the fusion polynucleotide in a selected host cell results in a specific phenotype and the presence of the reporter; mutagenizing the test nucleic acid construct to provide a mutagenized construct; transforming a selected host cell with the mutagenized construct to provide a transformed host cell; selecting a transformed host cell that exhibits the reporter, but which does not exhibit the specific phenotype; and sequencing a portion of the mutagenized construct from the selected transformed host cell to determine the alteration of the polynucleotide(s).

Abstract: Compounds of formula 1 modulate the activity of Rho C: wherein n is 2 to 5, inclusive; R1, R2, R3, R4, R5, R6, R7, R8, and R9 are each independently H, halo, lower alkyl, lower alkoxy, lower alkylamino, trifluoromethyl, nitro, lower alkylthio, or two adjacent residues form cycloalkyl, cycloalkenyl, aryl, or lower alkylenedioxy; and pharmaceutically acceptable salts thereof.

Abstract: Compounds of formula 1 are effective modulators of p38 MAP kinase. wherein R1 is H, lower alkyl, or OR5, where R5 is aryl, heterocyclyl, acyl, N—R6-4-piperidinyl, N—R6-4-piperidinylmethyl, or N—R6-4-pipelidinylethyl, where aryl and heterocyclyl are substituted with 1-3 R6 substituents selected from the group consisting of H, lower alkyl, lower alkenyl, OH, NO2, NH2, halo, trihalomethyl, —CN, SH, SO, SO2, SO3H, —OR, —COR, —COOR, —CONHR, —OCOR, and —NCOR, where R is lower alkyl; R2 is H or lower alkyl; R3 is aryl substituted with 1-3 R6 substituents; R4 is H, lower alkyl, aryl, aralkyl, —OH, —NH2, —NHR, or —OR, where R is lower alkyl or aryl-lower alkyl; and A is —CH— or —N—; and pharmaceutically acceptable salts thereof.

Abstract: Vectors of the invention facilitate selection of host cells having operably incorporated query genes, and substitution of the query gene with a different gene.

Abstract: Compounds of the invention have the structure D—L—A*, where L is a linking moiety that maintains D and A in a configuration compatible with FRET, D is a fluorescent donor moiety capable of causing an acceptor moiety to fluoresce by FRET, and A* is a fluorescent acceptor moiety capable of accepting energy from the donor moiety by FRET and fluorescing only after cleavage of one or more labile groups to provide acceptor A. These compounds are useful as fluorescent substrates for detection of enzymes in vivo.

Abstract: Methods and nucleic acid constructs for testing and validating activity reporter cells, using a plurality of host cell genes, are described.

Abstract: A two-step, scalable method is described for identifying the cellular function(s) of one or more genes of unknown function, and for identifying modulators of the gene(s). The method uses the reversal or alteration of a phenotype created by the expression of the heterologous gene, e.g., a human gene, to identify modulators of that gene's activity. That modulator is then used in an in vitro or in vivo disease model system to identify compounds which affect disease progression. The subset of compounds which influence disease in a therapeutic manner are drug leads. However, all compounds which influence disease progression are tools to at least partially characterize gene function. The inhibitor identification step of the method is preferably carried out using a plurality of microbial strains or cell lines expressing different heterologous DNA sequences in a single solution. The method is particularly useful for genes which have not been validated as good inhibitor targets.