22 research outputs found
Protection of the Baltic biocenoses against pollution and their long-term changes
Meeting: World Commission on Environment and Development, Public Hearing, 8, 11 Dec. 1986, Moskva, SURelated to DAP 87-4249 under which IDRC supported the WCED to acquire and duplicate original papers, submissions, tapes and transcripts, became the depository of all original archival materials and received the right to microfiche the collection for broader disseminatio
Influence of Temperatures on the Tautomerism of the N-(1H-imidazoline-2-yl)-1H-benzimidazol-2-amine and Investigation of Its Electrochemical Behaviour
Direct detection of the hydrolysis of nerve agent model compounds using a fluorescent probe
Synthesis and SAR of <i>b</i>‑Annulated 1,4-Dihydropyridines Define Cardiomyogenic Compounds as Novel Inhibitors of TGFβ Signaling
A medium-throughput murine embryonic stem cell (mESC)-based
high-content
screening of 17000 small molecules for cardiogenesis led to the identification
of a <i>b</i>-annulated 1,4-dihydropyridine (1,4-DHP) that
inhibited transforming growth factor β (TGFβ)/Smad signaling
by clearing the type II TGFβ receptor from the cell surface.
Because this is an unprecedented mechanism of action, we explored
the series’ structure–activity relationship (SAR) based
on TGFβ inhibition, and evaluated SAR aspects for cell-surface
clearance of TGFβ receptor II (TGFBR2) and for biological activity
in mESCs. We determined a pharmacophore and generated 1,4-DHPs with
IC<sub>50</sub>s for TGFβ inhibition in the nanomolar range
(e.g., compound <b>28</b>, 170 nM). Stereochemical consequences
of a chiral center at the 4-position was evaluated, revealing 10-
to 15-fold more potent TGFβ inhibition for the (+)- than the
(−) enantiomer. This stereopreference was not observed for
the low level inhibition against Activin A signaling and was reversed
for effects on calcium handling in HL-1 cells
Novel approaches to mitigating parathion toxicity: targeting cytochrome P450-mediated metabolism with menadione
1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells
Inhibition of Protein Kinase C-Driven Nuclear Factor-κB Activation: Synthesis, Structure−Activity Relationship, and Pharmacological Profiling of Pathway Specific Benzimidazole Probe Molecules
A unique series of biologically active chemical probes that selectively inhibit NF-κB activation induced by protein kinase C (PKC) pathway activators have been identified through a cell-based phenotypic reporter gene assay. These 2-aminobenzimidazoles represent initial chemical tools to be used in gaining further understanding on the cellular mechanisms driven by B and T cell antigen receptors. Starting from the founding member of this chemical series <b>1a</b> (notated in PubChem as CID-2858522), we report the chemical synthesis, SAR studies, and pharmacological profiling of this pathway-selective inhibitor of NF-κB activation