Abstract: The invention provides a compound of formula (I): (I) wherein R1-R4 have any of the values defined in the specification, as well as compositions comprising a compound of formula (I) and methods for treating diseases (e.g. cancer).

Abstract: The invention provides a compound of formula (I): (I) wherein R1-R4 have any of the values defined in the specification, as well as compositions comprising a compound of formula (I) and methods for treating diseases (e.g. cancer).

Abstract: Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

Abstract: Methods for identifying compounds that inhibit or stimulate the autophagy pathway are described. Devices for detecting the expression of autophagy-related genes and kits for assaying the expression of autophagy-related genes are also described. Also described are methods for identifying individuals susceptible to or afflicted with a disease state associated with an autophagy pathway defect.

Abstract: Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

Abstract: Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

Abstract: Compounds of formulas I-IV: (I), (II), (III) (IV), wherein: R1 and R4-R23 are independently selected from H and 1-3 carbon lower alkyl; and R2 and R3 are independently selected from H, 1-3 carbon lower O II alkyl, and —C—Ra, wherein Ra is 1-3 carbon lower alkyl. Pharmaceutical compositions, which include any of Compounds I-IV and a pharmaceutically acceptable carrier, methods of inducing tumor cell apoptosis by administering to a patient in need thereof an effective amount of any of Compounds I-IV, and methods for obtaining any of Compounds I-IV by extracting the compound from coral are also provided.

Abstract: Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.

Abstract: Ribonucleases, antibiotics, bacterial toxins and viruses inhibit protein synthesis, which results in apoptosis in mammalian cells. How the BCL-2 family of proteins regulates apoptosis in response to shutoff of protein synthesis is not known. According to the present invention, an Escherichia coli toxin MazF inhibited protein synthesis by cleavage of cellular mRNA, and induced apoptosis in mammalian cells. MazF-induced apoptosis required proapoptotic BAK and its upstream regulator, the proapoptotic BH3-only protein NBK/BIK, but not BIM, PUMA or NOXA. Furthermore, NBK/BIK- or BAK-deficient cells were resistant to cell death induced by pharmacologic inhibition of translation and by virus-mediated shutoff of protein synthesis. Thus, the BH3-only protein NBK/BIK is the apical regulator of a BAK-dependent apoptotic pathway in response to shutoff of protein synthesis.

Abstract: This invention provides recombinant cell lines and screening methods useful for identifying agents that induce apoptosis in target cells and therefore may be used to advantage in the treatment of neoplastic disorders.

Abstract: The present invention is a method for determining if a compound potentially modulates the ability of a putative oncogene to suppress p53-mediated effects, comprising (A) adding an amount of said compound to genetically engineered cells that express (i) a gene product that induces p53 mediated apoptosis; (ii) a gene product for a p53 gene, wherein either the gene or the gene product are externally controllable; and (iii) a putative oncogene that inhibits the effect of the gene product that induces p53 mediated apoptosis, and (B) examining said cells to determine whether apoptosis has occurred. In particular, the invention provides a method wherein said gene product that induces p53 mediated apoptosis is adenovirus gene E1A, wherein said externally controllable p53 gene product is a temperature-sensitive mutant of p53, and wherein the putative oncogene is selected from the group bcl-2, ras, or the adenovirus E1B(19K) gene.