Journal: Marine Drugs

Article Title: The Chemistry and Pharmacology of Anatoxin-a and Related Homotropanes with respect to Nicotinic Acetylcholine Receptors

doi:

Figure Lengend Snippet: The Novo Nordisk (1999–2001) nicotinic pharmacophore (as applied to nicotine) [ – ].

Article Snippet: When studied against the Novo Nordisk pharmacophore, the “best fit” for 23 was found for the s-trans conformer (as shown in ) although a binding mode via the s-cis arrangement could not be ruled out.

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Journal: Molecules

Article Title: Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors

doi: 10.3390/molecules24061098

Figure Lengend Snippet: Ligand-based approaches leading to identification of new mGlu 2 PAMs. ( a ) The structural alignment and pharmacophore of selected mGlu 2 receptor PAMs. ( b ) The electrostatic fields showing the similarity between pyridone and subsequent imidazopyridine and triazopyridine scaffolds.

Article Snippet: As mentioned in the mGlu 1 section, scientists from Merz Pharmaceuticals built a pharmacophore model for mGlu 1 allosteric modulators based on previously described ligands [ , ].

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Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Formoterol exposure increases uncoupled OCR and mtDNA copy number in RPTC and AFC. A, RPTC were exposed to isoproterenol (nonspecific β-AR agonist), BRL 37344 (β3-AR agonist), and formoterol (β2-AR agonist) for 24 h and evaluated for changes in FCCP-OCR. B, AFC were exposed to isoproterenol (nonspecific β-AR agonist), BRL 37344 (β3-AR agonist), and formoterol (β2-AR agonist) for 24 h and evaluated for changes in FCCP-OCR. C, RPTC were exposed to the nonspecific β-AR agonists dopamine, epinephrine, and norepinephrine for 24 h and evaluated for changes in FCCP-OCR. D, RPTC were exposed to 30 nM formoterol for 24 h and evaluated for changes in mtDNA copy number relative to DMSO controls. Data are represented as mean ± S.E.M. of four biological replicates. *, P < 0.05.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

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Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Formoterol exposure induced the expression of mitochondrial genes and mtDNA copy number in the kidney cortex of CB57BL/6 mice. A, mRNA expression was evaluated in the kidney cortex of CB57BL/6 mice 24 h after a single intraperitoneal injection with 100 μg/kg formoterol. B, mRNA expression was evaluated in the kidney cortex of CB57BL/6 mice 72 h after daily repeated intraperitoneal injections with 100 μg/kg formoterol. C, mtDNA copy number was evaluated in the kidney cortex 24 and 72 h after daily repeated intraperitoneal injection with 100 μg/kg formoterol. Values indicate fold change relative to DMSO controls. Data are represented as mean ± S.E.M. of three to six biological replicates. *, P < 0.05.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

Techniques: Expressing, Injection

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Formoterol exposure induced the expression of mitochondrial genes and mtDNA copy number in the hearts of CB57BL/6 mice. A, mRNA expression was evaluated in the hearts of CB57BL/6 mice 24 h after a single intraperitoneal injection with 100 μg/kg formoterol. B, mRNA expression was evaluated in the hearts of CB57BL/6 mice 72 h after daily repeated intraperitoneal injections with 100 μg/kg formoterol. C, mtDNA copy number was evaluated in the heart 24 and 72 h after daily repeated intraperitoneal injection with 100 μg/kg formoterol. Values indicate fold change relative to DMSO controls. Data are represented as mean ± S.E.M. of three to six biological replicates. *, P < 0.05.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

Techniques: Expressing, Injection

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Formoterol pharmacophore extraction of the 1280-compound Sigma LOPAC Chemical fingerprints defined within the MOE software package were used to cluster compounds based on molecular similarity as measured from the TC. Analysis of the data using a TC of 60% identified 23 compounds of 1280 (or 1.8%) compounds from LOPAC that matched formoterol based on chemical similarity. RPTC were treated with the 23 identified LOPAC compounds (5 μM) for 24 h and examined for changes in FCCP-OCR. This assay identified nisoxetine, which increases FCCP-OCR 15% above vehicle control.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

Techniques: Extraction, Software, Control

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Cheminformatic analysis of formoterol identified nisoxetine, which induces MB in RPTC. A, RPTC were exposed to formoterol and nisoxetine (10–300 nM) for 24 h and examined for changes in FCCP-OCR. Values indicate a percentage of fold change relative to DMSO controls. Data are represented as mean ± S.E.M. of four biological replicates. B, pharmacophore based on the alignment of formoterol and nisoxetine. Formoterol and nisoxetine aligned with superimposed chemical features. F1 is a proton acceptor, F2 and F3 are hydrophobic, F4 is a mixed feature with a cationic and proton donor, and F5 and F6 are mixed features with aromatic or hydrophobic characteristics. F1 and F4 were marked as essential while requiring that at least five features matched the model. C, formoterol aligned with superimposed pharmacophore.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

Techniques:

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: The effects of formoterol and nisoxetine are inhibited by β2 antagonism. A, RPTC were pre-exposed to the β-AR antagonist propranolol (5 nM) 1 h before exposure to 30 nM formoterol or nisoxetine and evaluated for changes in FCCP-OCR. B, RPTC were pre-exposed to the β2-AR inverse agonist ICI-118,551 (3 and 10 nM) 1 h before exposure to 30 nM formoterol or nisoxetine and evaluated for changes in FCCP-OCR. Values indicate a percentage of fold change relative to DMSO controls. Data are represented as mean ± S.E.M. of four biological replicates. *, P < 0.05.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

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Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: The six-point formoterol pharmacophore model was used to search the ChemBridge DIVERSet for similar compounds The ChemBridge DIVERSet contains 50,080 unique drug-like compounds that cover pharmacophore diversity. These compounds were used to create a 1,420,467-entry conformer library. An in silico search identified 16 compounds (or 0.03%) containing all six chemical features with a RMSD < 1 Å to the pharmacophore model for all features. RPTC were exposed to the 16 identified ChemBridge compounds (5 μM) for 24 h and examined for changes in FCCP-OCR. This assay identified three novel compounds (CB1, CB2, and CB3) that increase FCCP-OCR 15% above the vehicle control.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

Techniques: In Silico, Control

Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC. A, RPTC were exposed to ChemBridge compounds 1, 2, and 3 (10–300 nM) for 24 h and evaluated for changes in FCCP-OCR. Values indicate a percentage of fold change relative to DMSO controls. Data are represented as mean ± S.E.M. of four biological replicates. B, refined pharmacophore based on the alignment of formoterol, nisoxetine, CB2, and CB3. In this alignment, F1 is a proton acceptor, F2 and F3 are hydrophobic, F4 is a mixed feature with a proton donor and a cationic or proton acceptor, and F5 and F6 are mixed features with aromatic or hydrophobic characteristics. F7 is a unique hydrophobic feature found in nisoxetine and CB2. F1, F2, F4, F5, and F6 are essential features. C, nisoxetine aligned with superimposed pharmacophore.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

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Journal: The Journal of Pharmacology and Experimental Therapeutics

Article Title: The ? 2 -Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis

doi: 10.1124/jpet.112.191528

Figure Lengend Snippet: Formoterol, nisoxetine, and (CB2) ChemBridge 5144525 The original pharmacophore was built by using formoterol and nisoxetine. CB1, CB2, and CB3 were found by using the original pharmacophore from a search of the ChemBridge DIVERSet 50,000 small-molecule conformational library. CB2 and CB3 were confirmed to be biogenic; however, CB2 was the only compound to add features to the pharmacophore model.

Article Snippet: Analysis of the final alignment revealed a unique hydrophobic feature (F7) found in nisoxetine and CB2 ( C; ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 Formoterol pharmacophore identified two ChemBridge compounds that induce MB in RPTC.

Techniques: