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  "documentTitle": "Harmony Biosciences (HRMY)",
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      "text": "Excerpts from a review paper evaluating virtually every H3R drug candidate that was attempted",
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      "text": "The reasons for the industry-wide failure of these H3R antagonist programs over several decades are voluminous: poor pharmacokinetic characteristics due to lack of bioavailability and/or a failure to penetrate the blood/brain barrier; a variety of off-target effects; and a broad toxicity profile.",
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      "text": "New developments around histamine H3 receptor antagonists/inverse agonists: a patent review (2010 – present)",
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      "text": "Generally, H3R as a drug target is not easy. So far, > 20 years after identification of the receptor and >15 years after cloning it, non-of-ligand has entered into the market. The complicated pharmacology of H3R makes this way difficult. Differences in results and species dependency (with largest between bH3R and rH3R) have hindered interpretation of preclinical studies. Also over 20 existing hH3R isoforms, with some having a different pharmacological profile may hamper understanding of the action of H3R ligands.",
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      "text": "The reasons for the industry-wide failure of these H3R antagonist programs over several decades are voluminous: poor pharmacokinetic characteristics due to lack of bioavailability and/or a failure to penetrate the blood/brain barrier; a variety of off-target effects; and a broad toxicity profile. In fact, the H3 receptor and its pharmacological interaction are poorly understood – a key reason being that there isn’t just “one” H3 receptor as it has 20 varieties called isoforms. In other words, H3 receptors are a class versus a single uniform target. The scientific understanding of these isoforms is primitive, and there has been little research into how different H3 isoforms interact with a single drug. A notable review paper evaluated virtually every compound tried by various pharma companies and attributed the failure to “the complicated pharmacology of H3R” and “over 20 existing hH3R isoforms, with some having a different pharmacological profile.”",
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      "text": "“the complicated pharmacology of H3R” and “over 20 existing hH3R isoforms, with some having a different pharmacological profile.” — New developments around histamine H3 receptor antagonists/inverse agonists: a patent review (2010 - present)",
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      "text": "Source: https://pubmed.ncbi.nlm.nih.gov/24131059/",
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