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  "documentTitle": "Harmony Biosciences (HRMY)",
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      "text": "As noted in a previous section, several pharmaceutical companies with H3R program synthesized pitolisant as part of their research, and specifically noted the drug's \"potential for phospholipidosis\" as one of many \"important hurdles for this novel compound.\"",
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      "text": "Whilst the majority of non-imidazole classes of H3R antagonists appear not to inhibit significantly the CYP family of enzymes, many H3R antagonist programmes have reportedly suffered from significant blockade of the hERG K+ channel [43–45] or have demonstrated the potential for phospholipidosis [43,46] or they have wrestled with P-gp substrate problems. As an example, Abbott's pre-clinical 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) that manifested itself in a dose-dependent QTc prolongation in dog (Altenbach, personal communication) and monkey [47]. In addition, the compound was also reported to cause phospholipidosis. The combination of these two factors is probably what led to the compound's demise.",
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      "text": "these species. BF2.649 is presently under clinical investigation in several Phase II trials for the treatment of schizophrenia, ADHD, dementia and Parkinson's disease. (www.stanleyresearch.org/programs/trialgrants.htm). From the development point of view, our laboratory findings suggest that CYP2D6 inhibition, potent hERG binding and the potential for phospholipidosis would likely be important hurdles for this novel compound.",
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      "text": "The literature on drug-induced phospholipidosis indicates that it is caused by a particular molecular feature shared by certain drugs (“cationic amphilic drugs”), and is inherent to H3 receptor antagonist/inverse agonist programs. As noted in a previous section, several pharmaceutical companies with H3R program synthesized pitolisant as part of their research, and specifically noted the drug’s “potential for phospholipidosis” as one of many “important hurdles for this novel compound.”",
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      "text": "\"potential for phospholipidosis\" — Abbott researchers (2008 paper). \"The combination of these two factors is probably what led to the compound's demise.\" — 2009 paper regarding ABT-239.",
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      "text": "Source https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483387/pdf/bjp2008147a.pdf; https://pubmed.ncbi.nlm.nih.gov/19429511/",
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      "text": "2009 paper indicated phospholipidosis-toxicity for non-imidazole-based H3R compounds like pitolisant",
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      "text": "2008 paper by Abbott researchers indicates they tested pitolisant: “potential for phospholipidosis”",
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