Incomudrox
New member
Was poking around the internet and found TOCRIS Biosciences site... I found it quite interesting. They have several compounds for Cl Ion channel transporting and blocking. Cool thing is you can buy them... if you are wealthy enough.
Almost forgot the link:<a href="http://www.tocris.com/pharmacologicalBrowser.php?ItemId=5032">http://www.tocris.com/pharmacologicalBrowser.php?ItemId=5032</a>
<span style="text-decoration: underline;"><strong>DCEBIO</strong> -Stimulates Cl<sup>-</sup>secretion via activation of hIK1 K<sup>+</sup>channels and the activation of an apical Cl<sup>-</sup>conductance. More potent than its analog1-EBIO(Cat. No. 1041).
<span><strong>Singh</strong><span><em>et al</em><span>(2001) Benzimidazolone activators of chloride secretion: potential therapeutics for cystic fibrosis and chronic obstructive pulmonary disease. J.Pharmacol.Exp.Ther.<em><strong>296</strong></em><span>600. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/11160649" target="resource_window">11160649</a><span>. <<
<span style="text-decoration: underline;"><strong>KM 11060</strong> -<span>Corrects F508del-CFTR trafficking; increases the amount of functional CFTR at the plasma membrane (~75%). Shown to inhibit PDE5 activity.
<span><strong>Robert</strong><span><em>et al</em><span>(2008) Structural analog of Sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect. Mol.Pharmacol.<em><strong>73</strong></em><span>478. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/17975008" target="resource_window">17975008</a><span>. <<
<span style="text-decoration: underline;"><strong>PG 01</strong> -<span>Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. Corrects gating defects of CFTR mutants such as<span class="symbol">Δ<span>F508 (K<sub>a</sub><span>= 0.3<span class="symbol">μ<span>M), E193K and G970R (K<sub>d</sub><span>values are 0.22<span class="symbol">μ<span>M and 0.45<span class="symbol">μ<span>M respectively). Increases<span class="symbol">Δ<span>F508-CFTR Cl<sup>-</sup><span>currents in the presence of forskolin; displays no effect on Ca<sup>2+</sup><span>-activated Cl<sup>-</sup><span>current.
<p class="marT5"><strong>Pedemonte</strong><em>et al</em>(2005) Phenylglycine and sulphonamide correctors of defective DF508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating. Mol.Pharmacol.<em><strong>67</strong></em>1797. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/15722457" target="resource_window">15722457</a>.
<p class="marT5"><strong>Caputo</strong><em>et al</em>(2009) Mutation-specific potency and efficacy of cystic fibrosis transmembrane conductance regulator chloride channel potentiators. J.Pharmacol.Exp.Ther.<em><strong>330</strong></em>783. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/19491324" target="resource_window">19491324</a>.
<p class="marT5"><strong>Pedemonte</strong><em>et al</em>(2010) Influence of cell background on pharmacological rescue of mutant CFTR. Am.J.Physiol.Cell Physiol<em><strong>298</strong></em>C866. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/20053923" target="resource_window">20053923</a>.
<p class="marT5">
<p class="marT5">However the one I found most intestesting was DCPIB. Oddly it is a Cl Channel BLOCKER. What they found it does in-vitro is inhibits glucose stimulated insulin secretion. HMMMMM. Let's think about that. If CF in our bodies normally would do this, is CFRD possibly related to high enough levels of a similar chemical in the body due to lack of Cl Transport on the CFTR what causes CFRD and that it is only because the secretion mechanism is shut off by this and nothing more? Possibly fluctuates from time to time giving us inconcistencies in BSG levels?
<p class="marT5">
<p class="marT5"><span><span style="text-decoration: underline;"><strong>DCPIB</strong> - Potent, selective blocker of the volume-sensitive anion channel (VSAC) in rat pancreatic<span class="symbol">β<span>-cells (IC<sub>50</sub><span>~ 2<span class="symbol">μ<span>M) and I<sub>Cl,swell</sub><span>in various cardiovascular tissues (IC<sub>50</sub><span>= 4.1<span class="symbol">μ<span>M in CPAE cells); blockade is voltage-independent. Displays minimal inhibition of other Cl<sup>-</sup><span>and K<sup>+</sup><span>currents (< 10% inhibition at 10<span class="symbol">μ<span>M). Inhibits glucose-stimulated insulin secretion in intact<span class="symbol">β<span>-cells via VSAC inhibition and indirect K<sub>ATP</sub><span>channel activation. Reverses cell swelling-induced action potential duration shortening in atrial myocytes and inhibits astroglial swelling<em>in vitro</em><span>.
<p class="marT5"><strong>Bourke</strong><em>et al</em>(1981) Adenosine-stimulated astroglial swelling in cat cerebral cortex<em>in vivo</em>with total inhibition by a non-diuretic acylaryloxyacid derivative. J.Neurosurg.<em><strong>55</strong></em>364. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/6267227" target="resource_window">6267227</a>.
<p class="marT5"><strong>Decher</strong><em>et al</em>(2001) DCPIB is a novel selective blocker of I<sub>Cl,swell</sub>and prevents swelling-induced shortening of guinea-pig atrial action potential duration. Br.J.Pharmacol.<em><strong>134</strong></em>1467. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/11724753" target="resource_window">11724753</a>.
<p class="marT5"><strong>Best</strong><em>et al</em>(2004) Inhibition of glucose-induced electrical activity in rat pancreatic β-cells by DCPIB, a selective inhibitor of volume-sensitive anion currents. Eur.J.Pharmacol.<em><strong>489</strong></em>13. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/15063150" target="resource_window">15063150</a>.
<span>
Almost forgot the link:<a href="http://www.tocris.com/pharmacologicalBrowser.php?ItemId=5032">http://www.tocris.com/pharmacologicalBrowser.php?ItemId=5032</a>
<span style="text-decoration: underline;"><strong>DCEBIO</strong> -Stimulates Cl<sup>-</sup>secretion via activation of hIK1 K<sup>+</sup>channels and the activation of an apical Cl<sup>-</sup>conductance. More potent than its analog1-EBIO(Cat. No. 1041).
<span><strong>Singh</strong><span><em>et al</em><span>(2001) Benzimidazolone activators of chloride secretion: potential therapeutics for cystic fibrosis and chronic obstructive pulmonary disease. J.Pharmacol.Exp.Ther.<em><strong>296</strong></em><span>600. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/11160649" target="resource_window">11160649</a><span>. <<
<span style="text-decoration: underline;"><strong>KM 11060</strong> -<span>Corrects F508del-CFTR trafficking; increases the amount of functional CFTR at the plasma membrane (~75%). Shown to inhibit PDE5 activity.
<span><strong>Robert</strong><span><em>et al</em><span>(2008) Structural analog of Sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect. Mol.Pharmacol.<em><strong>73</strong></em><span>478. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/17975008" target="resource_window">17975008</a><span>. <<
<span style="text-decoration: underline;"><strong>PG 01</strong> -<span>Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator. Corrects gating defects of CFTR mutants such as<span class="symbol">Δ<span>F508 (K<sub>a</sub><span>= 0.3<span class="symbol">μ<span>M), E193K and G970R (K<sub>d</sub><span>values are 0.22<span class="symbol">μ<span>M and 0.45<span class="symbol">μ<span>M respectively). Increases<span class="symbol">Δ<span>F508-CFTR Cl<sup>-</sup><span>currents in the presence of forskolin; displays no effect on Ca<sup>2+</sup><span>-activated Cl<sup>-</sup><span>current.
<p class="marT5"><strong>Pedemonte</strong><em>et al</em>(2005) Phenylglycine and sulphonamide correctors of defective DF508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating. Mol.Pharmacol.<em><strong>67</strong></em>1797. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/15722457" target="resource_window">15722457</a>.
<p class="marT5"><strong>Caputo</strong><em>et al</em>(2009) Mutation-specific potency and efficacy of cystic fibrosis transmembrane conductance regulator chloride channel potentiators. J.Pharmacol.Exp.Ther.<em><strong>330</strong></em>783. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/19491324" target="resource_window">19491324</a>.
<p class="marT5"><strong>Pedemonte</strong><em>et al</em>(2010) Influence of cell background on pharmacological rescue of mutant CFTR. Am.J.Physiol.Cell Physiol<em><strong>298</strong></em>C866. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/20053923" target="resource_window">20053923</a>.
<p class="marT5">
<p class="marT5">However the one I found most intestesting was DCPIB. Oddly it is a Cl Channel BLOCKER. What they found it does in-vitro is inhibits glucose stimulated insulin secretion. HMMMMM. Let's think about that. If CF in our bodies normally would do this, is CFRD possibly related to high enough levels of a similar chemical in the body due to lack of Cl Transport on the CFTR what causes CFRD and that it is only because the secretion mechanism is shut off by this and nothing more? Possibly fluctuates from time to time giving us inconcistencies in BSG levels?
<p class="marT5">
<p class="marT5"><span><span style="text-decoration: underline;"><strong>DCPIB</strong> - Potent, selective blocker of the volume-sensitive anion channel (VSAC) in rat pancreatic<span class="symbol">β<span>-cells (IC<sub>50</sub><span>~ 2<span class="symbol">μ<span>M) and I<sub>Cl,swell</sub><span>in various cardiovascular tissues (IC<sub>50</sub><span>= 4.1<span class="symbol">μ<span>M in CPAE cells); blockade is voltage-independent. Displays minimal inhibition of other Cl<sup>-</sup><span>and K<sup>+</sup><span>currents (< 10% inhibition at 10<span class="symbol">μ<span>M). Inhibits glucose-stimulated insulin secretion in intact<span class="symbol">β<span>-cells via VSAC inhibition and indirect K<sub>ATP</sub><span>channel activation. Reverses cell swelling-induced action potential duration shortening in atrial myocytes and inhibits astroglial swelling<em>in vitro</em><span>.
<p class="marT5"><strong>Bourke</strong><em>et al</em>(1981) Adenosine-stimulated astroglial swelling in cat cerebral cortex<em>in vivo</em>with total inhibition by a non-diuretic acylaryloxyacid derivative. J.Neurosurg.<em><strong>55</strong></em>364. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/6267227" target="resource_window">6267227</a>.
<p class="marT5"><strong>Decher</strong><em>et al</em>(2001) DCPIB is a novel selective blocker of I<sub>Cl,swell</sub>and prevents swelling-induced shortening of guinea-pig atrial action potential duration. Br.J.Pharmacol.<em><strong>134</strong></em>1467. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/11724753" target="resource_window">11724753</a>.
<p class="marT5"><strong>Best</strong><em>et al</em>(2004) Inhibition of glucose-induced electrical activity in rat pancreatic β-cells by DCPIB, a selective inhibitor of volume-sensitive anion currents. Eur.J.Pharmacol.<em><strong>489</strong></em>13. PMID:<a title="View abstract" href="http://www.ncbi.nlm.nih.gov/pubmed/15063150" target="resource_window">15063150</a>.
<span>