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Low molecular weight inhibitors of Myc–Max interaction and function
The results show that the yeast two-hybrid screen is useful for identifying compounds that can be exploited in mammalian cells and provides a means by which structural analogs, based upon these first-generation Myc–Max inhibitors, can be developed to enhance antitumor efficacy.
Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages
A temporal role for Dusp6 in restricting cardiac progenitors and controlling heart organ size was uncovered with BCI treatment at varying developmental stages, highlighting the power of in vivo zebrafish chemical screens to identify novel compounds targeting D Susp6, a component of the FGF signaling pathway that has eluded traditional high-throughput in vitro screens.
The Substrate Recognition Domains of the N-end Rule Pathway*
This work characterized substrate binding specificity and recognition domains of UBR proteins and proposed a model where the 70-residue UBR box functions as a common structural element essential for binding to all known destabilizing N-terminal residues, whereas specific residues localized in the U BR box or the N-domain provide substrate selectivity through interaction with the side group of an N-Terminal amino acid.
The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease.
It is demonstrated that T0901317 decreases amyloidogenic processing of APP in vitro and in vivo, thus supporting the search for potent and specific LXR ligands with properties allowing therapeutic application.
Overexpression of metallothionein confers resistance to anticancer drugs.
Tumor cell lines with acquired resistance to the antineoplastic agent cis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan.
microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells.
microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain
Potent and Selective Disruption of Protein Kinase D Functionality by a Benzoxoloazepinolone*
The discovery of the first potent and selective cell-active small molecule inhibitor for PKD, benzoxoloazepinolone (CID755673), which inhibited the known biological actions of PKD1 including phorbol ester-induced class IIa histone deacetylase 5 nuclear exclusion, vesicular stomatitis virus glycoprotein transport from the Golgi to the plasma membrane, and the ilimaquinone-induced Golgi fragmentation.
Chemical genetics of Plasmodium falciparum
A phenotypic forward chemical genetic approach to discover new antimalarial chemotypes and structures and biological activity of the entire library are disclosed, many of which showed potent in vitro activity against drug-resistant P. falciparum strains.
Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide.
Testing the hypothesis that overexpression of MT reduces the sensitivity of NIH 3T3 cells to the .NO donor, S-nitrosoacetylpenicillamine (SNAP), and to .NO released from cells after infection with a retroviral vector expressing human iNOS gene shows results consistent with a role for cytoplasmic MT in interacting with .NO and reducing .NO-induced cyto- and nuclear toxicity.
Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25.
Using a chemical complementation assay, it was found that NSC 663284 blocked cellular Erk dephosphorylation caused by ectopic Cdc25A expression, and computational electrostatic potential mapping suggested the need for an electron-deficient 7-position for maximal inhibitor activity.