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-10772849-B2
Publication Date
2020-09-15
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 invention discloses the use of specific fenoterol analogues, such as (R,R′)-4′-methoxy-1-naphthylfenoterol (MNF) and related compounds, as modulators of cannabinoid (CB) receptor activity to regulate disorders and diseases associated with dysregulated CB receptors. The methods include administering effective amounts of these fenoterol analogues to subjects having or at risk of developing disorders regulated by CB receptor activity, thereby reducing symptoms like tumor growth. The compounds are capable of treating cancers including glioblastoma, hepatocellular carcinoma, liver, colon, and lung cancer, which are associated with altered CB receptor activity or expression, particularly targeting the GPR55 cannabinoid receptor.
The problem addressed by this invention arises from the increasing incidence and mortality of various cancers, especially brain and liver cancers, for which there are currently no effective clinical treatments. Traditional treatments often fail, and there is an urgent need for novel therapeutic agents that can modulate CB receptor activity and effectively inhibit tumor growth and progression. The discovery that fenoterol analogues can act as CB receptor modulators opens avenues for treating these CB receptor-related diseases.
The innovation involves the identification that certain fenoterol analogues, initially known as β2-adrenergic receptor agonists, unexpectedly inhibit tumor cell proliferation through modulation of cannabinoid receptor signaling, specifically GPR55. The compounds can be formulated into pharmaceutical compositions and administered by various routes, including oral and parenteral. They demonstrate selective inhibition of tumor growth and metastasis, induce apoptosis, modulate gene expression related to cell cycle regulation, and cross the blood-brain barrier, providing effective central nervous system penetration for brain tumor treatment.
Claims Coverage
The claims include one independent claim focused on a method of treating colon cancer regulated by cannabinoid receptor activity, comprising administering a therapeutically effective amount of a fenoterol analogue compound. The claim encompasses administration forms, dosage ranges, and combination therapies.
Use of specific fenoterol analogues to treat colon cancer regulated by cannabinoid receptor activity
Administering a therapeutically effective amount of a compound, specifically fenoterol analogues such as (R,R′)-4′-methoxy-1-naphthylfenoterol (MNF) or (R,S′)-MNF, to a subject with colon cancer regulated by CB receptor activity to reduce symptoms and inhibit cancer cell growth.
Reduction of tumor growth and metastasis in colon cancer
The treatment reduces one or more symptoms including tumor growth and metastasis associated with colon cancer.
Targeting GPR55 as the cannabinoid receptor
The compound specifically targets the GPR55 cannabinoid receptor to exert therapeutic effects.
Combination therapy with additional chemotherapeutic agents
The method includes administering additional chemotherapeutic agents prior to, concurrently with, or subsequent to the fenoterol analogue treatment.
Administration via pharmaceutical compositions
The compound is administered as pharmaceutical compositions comprising a pharmaceutically acceptable carrier, including injectable fluids and oral dosage forms like syrups, tablets, capsules, powders, or suspensions.
Specified dosage forms and administration regimens
Pharmaceutical compositions contain about 1.0 to 50 mg of the compound for oral administration with doses given two to four times a day; parenteral administration dosage ranges from about 1 mg/kg to 100 mg/kg body weight.
The claims cover methods of treating colon cancer regulated by cannabinoid receptor activity using therapeutically effective fenoterol analogues that inhibit tumor growth via GPR55 modulation, including specified formulations, administration routes, dosage regimens, and optional combination with other chemotherapeutic agents.
Stated Advantages
Fenoterol analogues provide effective inhibition of tumor growth and metastasis in cancers associated with altered cannabinoid receptor activity.
The compounds are capable of penetrating the blood-brain barrier, allowing treatment of brain tumors such as glioblastoma.
The fenoterol analogues induce apoptosis and modulate gene expression related to cell cycle control in tumor cells.
The invention enables selective targeting of the GPR55 cannabinoid receptor, which is implicated in oncogenesis, leading to improved therapeutic outcomes.
Fenoterol analogues exhibit minimal off-target toxicity and lack significant negative effects on central nervous system function.
Documented Applications
Treatment of tumors and cancers regulated by cannabinoid receptor activity, including glioblastoma, hepatocellular carcinoma, liver cancer, colon cancer, lung cancer, prostate cancer, pancreatic cancer, and CNS tumors.
Use as chemotherapeutic agents to reduce tumor cell proliferation, induce apoptosis, and inhibit tumor growth and metastasis.
Treatment of disorders regulated by cannabinoid receptors such as diabetes, obesity, inflammatory diseases, pain disorders, bone loss, muscle wasting, osteoarthritis, Alzheimer's disease, depression, and anxiety.
Pharmaceutical compositions usable for oral or parenteral administration to human and veterinary subjects for reducing symptoms associated with these diseases.
Use as an adjuvant therapy following surgical resection, radiation, or chemotherapy to prevent tumor recurrence.
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