{'fraction_non_alphanumeric': 0.0192195690157251, 'fraction_numerical': 0.027373325567850902, 'mean_word_length': 5.557251908396947, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Therapeutic use of nucleotides in respiratory and ophthalmic diseases

Nucleotide agonists of P2Y2 receptors are potentially useful therapeutics for treating respiratory diseases such as chronic bronchitis and cystic fibrosis, and for treating ophthalmic indications such as dry eye and retinal detachment. INS365 is a chemically stable nucleotide P2Y2 agonist that, when inhaled, enhances mucociliary clearance of the airways and thus may be useful for treating chronic bronchitis in which retained mucus is a hallmark. On the ocular mucosa, P2Y2 agonists stimulate the secretion of salt, water, and mucus. This mechanism of basal tear secretion forms the scientific basis for the clinical investigation of INS365 as a tear film secretagogue for the treatment of dry eye disease. INS365 ophthalmic solution is currently in Phase II clinical trials in the US. INS37217, a next‐generation nucleotide P2Y2 agonist with enhanced metabolic stability and a potentially longer duration of action, is being developed for the treatment of cystic fibrosis and retinal detachment. In cystic fibrosis, P2Y2 agonists activate an alternative chloride channel, thereby restoring hydration of the airway surface and promoting mucociliary clearance. In experimental models of retinal detachment, INS37217 injected into the back of the eye activates P2Y2 receptors on the retinal pigmented epithelium, promoting fluid absorption in the subretinal space and thus facilitating retinal reattachment. Since receptors for nucleotides are found throughout the body, nucleotides and their analogs have great therapeutic promise when administered locally to the desired site of action. Drug Dev. Res. 52:196–201, 2001. © 2001 Wiley‐Liss, Inc.