Methods of regulating cannabinoid receptor activity-related disorders and diseases
Inventors
Wainer, Irving W. • Bernier, Michel • Paul, Rajib K.
Assignees
US Department of Health and Human Services
Publication Number
US-10485771-B2
Publication Date
2019-11-26
Expiration Date
2033-05-23
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Abstract
This disclosure concerns the discovery of the use of fenoterol analogues for regulating cannabinoid (CB) receptor activity-related disorders and disease, such as dysregulated CB receptors, including treating a disorder or disease, such as a glioblastoma, hepatocellular carcinoma, liver cancer, colon cancer, and/or lung cancer, which is associated with altered cannabinoid receptor activity. In one example, the method includes administering to a subject having or at risk of developing a disorder or disease regulated by CB receptor activity an effective amount of a fenoterol analogue to reduce one or more symptoms associated with the disorder or disease regulated by CB receptor activity.
Core Innovation
This disclosure concerns the discovery of fenoterol analogues as cannabinoid (CB) receptor modulators capable of regulating CB receptor activity-related disorders and diseases, including treating tumors such as glioblastoma and hepatocellular carcinoma that are associated with altered CB receptor activity or expression, in particular of the GPR55 cannabinoid receptor. The method includes administering an effective amount of a fenoterol analogue to a subject having or at risk of developing a disorder or disease regulated by CB receptor activity to reduce one or more associated symptoms.
The inventors discovered that administration of specific fenoterol analogues inhibits one or more signs or symptoms such as tumor growth in tumors that express a CB receptor, including glioblastoma, hepatocellular carcinoma, liver cancer, colon cancer, and lung cancer. The compounds disclosed have specific chemical formulas with defined substituents and stereochemistry. Administration methods include pharmaceutical compositions containing these analogues alone or in combination, with possible co-administration of other therapeutic agents.
Background information establishes that cancer, including brain and liver cancers, are serious diseases lacking effective clinical treatments. Elevated mortality rates underline the need for novel therapies. The unique discovery that specific fenoterol analogues act as CB receptor modulators addresses this problem by providing new treatments for CB receptor-modulated disorders, particularly certain cancers.
Claims Coverage
The claims include one independent claim covering a method of treating liver cancer regulated by CB receptor activity with a specified compound, with several dependent claims detailing compound types, effects, and administration forms.
Method of treating liver cancer regulated by cannabinoid receptor activity
Administering a therapeutically effective amount of a defined fenoterol analogue compound to a subject with liver cancer regulated by CB receptor activity to reduce symptoms by inhibiting cancer cell growth.
Use of specific fenoterol analogues
Employing (R,R′)-4′-methoxy-1-naphthylfenoterol (MNF), (R,S′)-MNF, or combinations thereof as the compound administered.
Reducing tumor growth and metastasis
The treatment reduces tumor growth, metastasis, or both as clinical outcomes.
Targeting GPR55 cannabinoid receptor
The composition targets the CB receptor GPR55 involved in liver cancer activity.
Treatment of hepatocellular carcinoma
The method applies specifically to hepatocellular carcinoma among liver cancers.
Combination with additional chemotherapeutic agents
The method can include administering additional chemotherapeutic agents before, during, or after fenoterol analogue administration.
Pharmaceutical composition administration
Administering the compound as a pharmaceutical composition including pharmaceutically acceptable carriers.
Formulations for administration
Using injectable fluids or oral dosage forms such as syrups, solutions, suspensions, powders, pills, tablets, or capsules.
Dosage forms and amounts
Oral dosage forms containing about 1 to 50 mg compound, administered two to four times daily as tablets.
Therapeutically effective oral dosage ranges
Oral administration of the compound in amounts ranging from 0.001 mg/kg to 10 mg/kg body weight in single or divided doses.
Parenteral administration and dosages
Injectable formulations administered parenterally at dosages from about 1 mg/kg to 100 mg/kg body weight.
The claims focus on a therapeutic method of treating liver cancer regulated by cannabinoid receptor activity using fenoterol analogues, particularly targeting GPR55, specifying compounds, administration routes, dosages, and combinations with other agents.
Stated Advantages
Fenoterol analogues, such as MNF, demonstrate the capability to inhibit tumor cell growth and proliferation in various cancers including glioblastoma and hepatocellular carcinoma.
MNF crosses the blood-brain barrier enabling treatment of brain tumors without significant negative effects on central nervous system function.
These compounds provide a new therapeutic approach for cancers lacking effective clinical treatments, offering potential for reduced tumor size and metastasis.
Fenoterol analogues offer dual activity as β2-AR agonists and cannabinoid receptor modulators, potentially providing cardio-protective effects alongside antitumor activity.
Documented Applications
Treatment of disorders or diseases regulated by cannabinoid receptor activity, including glioblastoma, hepatocellular carcinoma, liver cancer, lung cancer, colon cancer, brain cancer, diabetes, and inflammatory diseases.
Methods of reducing or inhibiting tumor growth, tumor volume, or related symptoms in subjects having tumors expressing CB receptors such as GPR55.
Use of fenoterol analogues as chemotherapeutic agents, either alone or in combination with additional therapies including other chemotherapeutic agents, radiotherapy, or surgical tumor resection.
Treatment of metabolic disorders such as obesity and diabetes by modulating CB receptor activity.
Treatment of inflammatory and neuropathic pain disorders, and diseases associated with aging such as Alzheimer's disease, bone loss, muscle wasting, osteoarthritis, depression, and anxiety.
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