A major challenge to broadening oncology applications for inhibitors of the ubiquitin-proteasome system (UPS) is the identification of UPS-dependent cancer pathways predictive of tumors responsive to peptidomimetic inhibitors of its 20S core protease activity. To inform clinical studies evaluating UPS inhibitors as breast cancer therapeutics, seven phenotypically diverse human breast cancer cel...

Adrenergic response following infusions of yohimbine or normal saline was evaluated in 9 control subjects, 8 patients suffering from a major depressive episode (MDE), and 12 patients suffering from concurrent MDE and panic disorder (MDE + P). Blood was drawn at -20, 0, 5, 10, 20, 45, and 90 min following the infusions, and assayed for norepinephrine (NE) and 3-methoxy-4-hydroxy-phenyl glycol (M...

New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO2, NH2, OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine "cores" (3a,3b) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO2 ...

In the gerbil cerebral infarction was produced by unilateral carotid ligation. 3.5 hours later, when the neurological deficit was fully developed, hemisphere dopamine (DA) showed little change from normal. It seems unlikely that changes in DA are the direct cause of the turning behavior shown by these animals. Slight changes in norepinephrine (NE) occurred on the operated side but 4 hydroxy-3-m...

Potent ROCK inhibitors of a new class of 1-benzyl-3-(4-pyridylthiazol-2-yl)ureas have been identified. Remarkable differences in activity were observed for ureas bearing a benzylic stereogenic center. Derivatives with hydroxy, methoxy and amino groups at the meta position of the phenyl ring give rise to the most potent inhibitors (low nM). Substitutions at the para position result in substantia...

The structure of the title compound (4BPBA), C(13)H(9)BrO(2), is similar to that of phenyl benzoate (PBA), 4-methyl-phenyl benzoate (4MePBA) and 4-methoxy-phenyl benzoate, with somewhat different bond parameters. The dihedral angle between the phenyl and benzoyl rings in 4BPBA is 58.43 (17)°, compared with values of 55.7° in PBA and 60.17 (7)° in 4MPBA. The mol-ecules in the title compound are ...

Metabolomics represents an emerging discipline concerned with comprehensive assessment of small molecule endogenous metabolites in biological systems and provides a powerful approach insight into the mechanisms of diseases. Type 2 diabetes (T2D), called the burden of the 21st century, is growing with an epidemic rate. However, its precise molecular mechanism has not been comprehensively explore...

New evidence is presented for the mechanism of this reaction, which is used in estimating lipids. The reaction occurs in two stages: (a) Stage 1 evidently involves an oxidation step, forming a specific type of carbonium ion called an alkenyl cation of the general formula R--C+--C==C--R' (previous evidence had indicated that a carbonium ion of general formula R--C+--R' was formed by protonation ...

In the title compound, C(21)H(19)N(3)O(4), the central benzene ring makes dihedral angles of 78.54 (6) and 75.30 (6)° with the pyridine and 3-methoxy-phenyl rings, respectively. An intra-molecular N-H⋯N interaction occurs, generating an S(?). The crystal packing shows inter-molecular N-H⋯O hydrogen-bonding inter-actions between the N-H groups and the O atoms of the 3-methoxy-phenyl ring and the...

Novel curcumin analogues with α,β-unsaturated ketone moiety and/or α,β-saturated ketone structure were synthesized from curcumin via alkylation at the central carbon and the phenolic hydroxy groups, and hydrogenation of α,β-unsaturated ketone moiety. The antiproliferative activities were tested in five human solid tumor cell lines in vitro. Most of the compounds exhibited increased antiprolifer...