Endoplasmic-reticulum associated degradation (ERAD) is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY*) was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome...

The asymmetric unit of the title compound, [Co(NO3)2L] n , L = N-(pyridine-2-ylmeth-yl)pyridine-3-amine (C11H11N3), contains one CoII centre, two nitrate anions and one L ligand in which the Cpy-C-N-Cpy moiety adopts a trans conformation with a torsion angle of -173.1 (3) Å. The coordination geometry of the CoII atom is a distorted penta-gonal bipyramid. One amine N atom from the L ligand and f...

Cocrystallization of 4-carboxy-pyridine (4-CPY) and 5-sulfosalicylic acid (5-H(2)SSA) yields the title salt, C(6)H(6)NO(2) (+)·C(7)H(5)O(6)S(-). In the crystal structure, the components of the salt are linked by a combination of inter-molecular O-H⋯O and N-H⋯O, and weak C-H⋯O hydrogen bonds, forming a three-dimensional framework.

Erlotinib (ELT), a tyrosine kinase inhibitor, is widely used for the treatment of nonsmall cell lung cancer in clinic. Unfortunately, severe drug-induced liver injury and other adverse effects occurred during the treatment. Meanwhile, ELT has been reported to be a mechanism-based inactivator of cytochrome P450(CYPs) 3A4 and 3A5. The objectives of this study were to identify ketene intermediate ...

The in vitro metabolism of buprenorphine was investigated to explore new metabolic pathways and identify the cytochromes P450 (P450s) responsible for the formation of these metabolites. The resulting metabolites were identified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In addition to norbuprenorphine, two hydroxylated buprenorphine (M1 and M2) and three hydroxyl...

We determined the contribution of cytochrome P450 (CYP) isoforms to the metabolism of midazolam by kinetic analysis of human liver microsomes and CYP isoforms and by examining the effect of chemical inhibitors and monoclonal antibodies against CYP isoforms in vitro. Midazolam was metabolized to 1'-hydroxymidazolam (1'-OH MDZ) by human liver microsomes with a Michaelis-Menten constant (Km) of 4....

The Cytochrome P450 (CYP) proteins are a family of membrane bound proteins that function as a major metabolizing enzyme in the human body. Quantification of CYP induction is critical in determining the disposition, safety and efficacy of drugs in humans. Described is a gel-free, high-throughput LC-MS approach to quantitate the CYP isoforms 1A2, 2B6, 3A4 and 3A5 by measuring isoform specific pep...

The multivesicular body (MVB) sorting pathway is required for a number of biological processes, including downregulation of cell-surface proteins and protein sorting into the vacuolar lumen. The function of this pathway requires endosomal sorting complexes required for transport (ESCRT) composed of class E vacuolar protein sorting (Vps) proteins in Saccharomyces cerevisiae, many of which are co...

The asymmetric unit of the title compound, [Cd2(C7H4NO4)4(C6H4N2)4], contains one CdII atom, two 3-nitro-benzoate (NB) anions and two 3-cyano-pyridine (CPy) ligands. The two CPy ligands act as monodentate N(pyridine)-bonding ligands, while the two NB anions act as bidentate ligands through the carboxyl-ate O atoms. The centrosymmetric dinuclear complex is generated by application of inversion s...