Abstract: The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

Abstract: The present invention relates to the identification of provided cyclohexane-1,3-diones (CHD compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided CHD compounds.

Abstract: The present invention relates to the identification of inventive pyrimidine-2,4,6-triones (PYT compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the inventive PYT compounds.

Abstract: The present invention relates to the identification of provided cyclohexane-1,3-diones (CHD compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided CHD compounds.

Abstract: The present invention relates to the identification of inventive pyrimidine-2,4,6-triones (PYT compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the inventive PYT compounds.

Abstract: The present invention relates to the identification of provided cyclohexane-1,3-diones (CHD compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided CHD compounds.

Abstract: The present invention relates to the identification of provided cyclohexane-1,3-diones (CHD compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided CHD compounds.

Abstract: The present invention relates to the identification of inventive pyrimidine-2,4,6-triones (PYT compounds) and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the inventive PYT compounds.

Abstract: The present invention relates to the use of butaclamol and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.

Abstract: The present invention relates to the identification of compounds and pharmaceutical compositions thereof for treating subjects with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. The invention also provides methods of preparing the provided compounds.

Abstract: The invention provides a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal in need thereof which comprises administering to said mammal an effective amount of a substituted triazolopyrimidine derivative or a pharmaceutically acceptable salt thereof and further provides a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal in need thereof by interacting with tubulin and microtubules and promoting microtubule polymerization which comprises administering to said mammal an effective amount of a substituted triazolopyrimidine derivative or a pharmaceutically acceptable salt thereof.

Abstract: The invention provides a method of treating or inhibiting the growth of cancerous tumour cells and associated diseases in a mammal in need thereof which comprises administering to said mammal an effective amount of a substituted triazolopyrimidine derivative or a pharmaceutically acceptable salt thereof and further provides a method of treating or inhibiting the growth of cancerous tumour cells and associated diseases in a mammal in need thereof by interacting with tubulin and microtubules and promoting microtubule polymerization which comprises administering to said mammal an effective amount of a substituted triazolopyrimidine derivative or a pharmaceutically acceptable salt thereof.

Abstract: This invention discloses methods for identifying compounds, variant nuclear proteins and other auxiliary proteins that interfere with the Drosophila ultraspiracle protein ("Usp") and homologs thereof. The methods disclosed involve transformed yeast cells which contain a Usp binding partner, Usp or a homolog thereof which can bind with the Usp binding partner, and a reporter gene which requires a functional Usp--Usp binder partner complex for expression. The transformed yeast cells are incubated in the presence of a test compound to form a test culture and in the absence of a test compound to form a control culture. The expression of the reporter gene is monitored in one example by exposing the test and control cultures to canavanine under conditions in which control cultures exhibit reduced growth and detecting test cultures in which growth is increased relative to growth of control cultures.

Abstract: The present invention is directed to a expression vectors and yeast cells transformed therewith containing a first heterologous nucleotide sequence which codes for a G protein-coupled receptor, for example, the somatostatin receptor, and a second nucleotide sequence which codes for all or a portion of a G protein .alpha..beta..gamma. complex. Said heterologous protein is physically expressed in a host cell membrane in proper orientation for both stereoselective binding of ligands, as well as functional interaction with G proteins on the cytoplasmic side of the cell membrane. In some embodiments, a nucleotide sequence encoding a heterologous or chimeric G.alpha. protein is expressed in conjunction with nucleotide sequences from the yeast G protein .beta..gamma. subunits. A second aspect of the present invention provides expression vectors and transformed yeast cells encoding chimeric yeast/heterologous G protein coupled receptors.

Abstract: A binary assay identifies agents that inhibit sterol .DELTA.14 reductase involved in ergosterol biosynthesis. In the primary screen, sterol .DELTA.14 reductase inhibition by a test sample is assayed by adding the test sample to a culture of Neurospora crassa having an erg-3 mutation and also to a culture of a strain having an erg-1 mutation, comparing the extent of growth inhibition after incubation in the two cultures, and identifying as positives those samples that show growth inhibition in the erg-3 culture exceeding that in the erg-1 culture. In the secondary screen, samples that test positive in the primary screen are reassayed by adding the test sample to a culture of a Saccharomyces cerevisiae strain into which has been introduced multiple copies of a gene encoding sterol .DELTA.14 reductase and also to a strain of S.

Abstract: A method for screening for sterol biosynthesis inhibitors of potential use as fungicides or antihypercholesterolemic agents identifies agents by the induction of lanosterol 14-.alpha.-demethylase, an enzyme in the biosynthetic pathway of ergosterol and cholesterol, in cultures containing the agents. In one screening test, test samples are incubated in a culture of a Saccharomyces cerevisiae strain sensitive to ergosterol biosynthesis and containing a gene fusion of a lanosterol 14-.alpha.-demethylase clone with a gene for bacterial .beta.-galactosidase. After incubation of the culture, an increase in lancsterol 14-.alpha.-demethylase activity is determined indirectly by measuring .beta.-galactosidase activity. The culture media contains a chromogenic substrate of .beta.-galactosidase such as orthonitrophenyl-.beta.-D-galactoside or 5-bromo-4-chloro-3-indoyl-.beta.-D-galactoside, so that active samples are identified by the production of colored product.

Abstract: A gene encoding Saccharomyces cerevisiae sterol .DELTA.14 reductase of the ergosterol biosynthetic pathway is isolated and cloned by selecting strains carrying sequences on a 2.mu. based vector for resistance to a morpholine fungicide such as fenpropimorph. Four distinct plasmid inserts which produce morpholine resistance are obtained, and one of these is characterized and sequenced. The purified and isolated DNA sequence encoding sterol .DELTA.14 reductase encodes a polypeptide exhibiting homology to the S. cerevisiae sterol C-24(28) reductase enzyme in the ergosterol biosynthetic pathway.

Abstract: A gene encoding Saccharomyces cerevisiae sterol .DELTA.14 reductase of the ergosterol biosynthetic pathway is isolated and cloned by selecting strains carrying sequences on a 2.mu. based vector for resistance to a morpholine fungicide such as fenpropimorph. Four distinct plasmid inserts which produce morpholine resistance are obtained, and one of these is characterized and sequenced. The purified and isolated DNA sequence encoding sterol .DELTA.14 reductase encodes a polypeptide exhibiting homology to the S. cerevisiae sterol C-24(28) reductase enzyme in the ergosterol biosynthetic pathway.

Abstract: A method for the identification of agents which inhibit spindle pole body formation or function, thus exhibiting selective fungicidal activity, involves the incubation of test samples in cultures of a Saccharomyces cerevisiae strain that produces excess numbers of spindle pole bodies. Cultures containing samples that inhibit spindle pole bodies exhibit enhanced growth because the growing yeast is rescued from the adverse effects of excess spindle bodies. In the preferred practice of the invention, the test sample is added to a S. cerevisiae culture or culture area containing a strain that has a conditional mutation producing excess spindle pole bodies, such as diploid esp1-1 strains. The culture or culture area is preincubated under permissive conditions wherein the strain can grow to some extent, and then conditions are shifted to restrictive conditions so that the mutant strain either cannot grow or grows poorly.

Abstract: A novel antibiotic substance, Scopularin, is prepared by cultivation of a strain of the microorganism, Scopulariopsis, A.T.C.C. No. 20,914. This compound and its alcohol derivative have also been found to have cytochrome P450 inhibition activity.