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      "text": "The paper graphically details the obvious similarity between the histamine H3 receptor and hERG blocker pharmacophores, illustrating why an H3 antagonist like pitolisant is inherently high risk for QT prolongation and cardiotoxicity.",
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      "text": "Visual comparison of hERG and H3 pharmacophore models",
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      "text": "Compounds that inhibit the H3R with high affinity contain a basic amine linked to an aromatic or general lipophilic region that is connected to either (1) a second basic site, (2) a polar group, (3) a lipophilic region, or (4) an acidic group, resulting in pharmacophores that comprise significant similarity to the predicted pharmacophore for hERG blockers (Fig. 1). As an example, Abbott's preclinical candidate ABT-239 (Table 1) is reported to exhibit strong binding to the hERG K+ channel (Ki = 0.45 nM; 420-fold selectivity H3R/hERG), which manifests itself in a dose-dependent QTc prolongation in dog (Altenbach, personal communication) and monkey.",
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      "text": "Compounds that inhibit the H3R with high affinity contain a basic amine linked to an aromatic or general lipophilic region that is connected to either (1) a second basic site, (2) a polar group, (3) a lipophilic region, or (4) an acidic group, resulting in pharmacophores that comprise significant similarity to the predicted pharmacophore for hERG blockers (Fig. 1). — Scientific paper excerpt",
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      "text": "Fig. 1. Comparison of the hERG and H3R pharmacophore models for nonimidazole H3R antagonists shown on the right. On the left, ABT-239 is docked into the hERG pore to show where the three main pharmacophore points are located. hERG, human Ether-à-go-go related gene channel; H3R, histamine H3 receptor.",
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