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      "text": "2009 paper by Evotec researchers indicates they tested pitolisant and that it was a disaster",
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      "text": "H3R antagonists/inverse agonists currently undergoing clinical evaluation\nBF2.649 (tiprolisant)\nBioprojet’s H3R antagonist BF2.649 (Table 2) exhibits potent binding to native human (IC50 = 5.3 nM), rat (Ki = 17 nM) and mouse (Ki = 14 nM) cortical H3 receptors. Further in vitro profiling in our laboratory (and others [15]) suggests that BF2.649 has both a CYP 2D6 liability (IC50 = 0.4 µM) and potent hERG K+ channel blockade (IC50 = 0.49 µM). BF2.649 is also reported to have poor PK profiles in both rat and dog (5% and 2% bioavailability, respectively [15]). Despite these issues, BF2.649 has been extensively profiled in pre-clinical animal models [62] and progressed into the clinic. Bioprojet recently reported the first clinical evi-",
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      "text": "Abbott’s comments were echoed in a 2009 paper by scientists at Evotec, a major drug development player that works with most of the world’s largest pharma companies. They indicated that they synthesized pitolisant in their laboratory, then known as BF2.649: “in vitro profiling in our laboratory (and others) suggests that BF2.649 has both a CYP 2D6 liability (IC50 = 0.4 mM) and potent hERG K+ channel blockade (IC50 = 0.49 mM).” They further indicated it has a poor pharmacokinetic profile with extremely low bioavailability.",
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      "text": "in vitro profiling in our laboratory (and others) suggests that BF2.649 has both a CYP 2D6 liability (IC50 = 0.4 µM) and potent hERG K+ channel blockade (IC50 = 0.49 µM). — Evotec researchers (2009 paper)",
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      "text": "The histamine H3 receptor as a therapeutic drug target for CNS disorders",
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