Methods and formulations for modulating Lyn kinase activity and treating related disorders
Inventors
Reaume, Andrew G. • Saporito, Michael S.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12070461-B2
Publication Date
2024-08-27
Expiration Date
Abstract
The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising the compounds or a pharmaceutically acceptable salts thereof that are useful in modulating lyn kinase activity, in particular, the compounds or a pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder including cardiovascular disease, dyslipidemia, dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e., Syndrome X), a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, type II diabetes, obesity, pancreatitis, hypertension, renal disease, inflammation, or impotence.
Core Innovation
The invention provides Lyn kinase-modulating compounds of Formulas I-VII, including a compound of Formula I, and pharmaceutically acceptable salts or prodrugs thereof. The compounds are defined by structural parameters including R1 as an alkyl group, X as a halogen, Y as O, S, or NH, Z as O or S, and integer constraints n from 0 to 5 and m of 0 or 1 with m+n less than or equal to 5.
The invention addresses the treatment or prevention of Lyn kinase-associated disorders, including metabolic syndrome (Syndrome X), dyslipidemia and dyslipoproteinemia, glucose metabolism disorders, obesity, cardiovascular disease, inflammation, septicemia, thrombotic disorders, renal diseases, pancreatitis, hypertension, cancer, and impotence. The document further emphasizes treatment for gestational diabetes mellitus (GDM) and maturity onset diabetes of the young (MODY) in a mammal.
A key aspect is therapeutic use in which the compound is administered concurrently with another therapeutic agent, including agents chosen from statins, PPAR agonists, bile-acid-binding resins, niacin or nicotinic acid, RXR agonists, anti-obesity drugs, hormones, insulin secretagogs, tyrophostines or sulfonylurea-based drugs, metformin, alpha-glucosidase inhibitors, apo A-I agonists, apolipoprotein E, cardiovascular drugs, and chemotherapeutic agents. In vitro and in vivo examples are described that include increased Lyn kinase activity and reduction of glucose and weight gain and reduced fat pad development in diabetic/obesity animal models.
Claims Coverage
The document includes one independent claim, covering a method of treating GDM or MODY using a specific Lyn-kinase-modulating compound of a parameterized formula, or a pharmaceutically acceptable salt, administered concurrently with a selected second therapeutic agent chosen from a specified list. Dependent claims further refine the structural definition, the chosen route and dose ranges, and the co-administered agent details such as enumerated drug examples and insulin formulation types.
Concurrent administration of a Lyn kinase modulating formula compound with another therapeutic agent for GDM or MODY
A method of treating gestational diabetes mellitus (GDM) or maturity onset diabetes of the young (MODY) in a mammal administering a compound of formula, with R1 as an alkyl group; X as a halogen; Y as O, S, or NH; Z as O or S; n an integer from 0 to 5; m 0 or 1; and m+n less than or equal to 5, or a pharmaceutically acceptable salt thereof, concurrently with another therapeutic agent chosen from a statin, a PPAR agonist, a bile-acid-binding resin, niacin, nicotinic acid, a RXR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a tyrophostine, a sulfonylurea-based drug, metformin, an alpha-glucosidase inhibitor, an apo A-I agonist, apolipoprotein E, a cardiovascular drug, and a chemotherapeutic agent.
The claim coverage centers on administering a parameterized Lyn kinase-modulating compound of Formula I, or a pharmaceutically acceptable salt, for treating GDM or MODY, with concurrent co-administration of a second therapeutic agent selected from multiple drug classes listed in the claim. Dependent claims further narrow the structural parameters and specify route-based administration and dosage ranges, and add more specific options for the co-administered agents, including injectable, transdermal, and inhaled insulin types.
Stated Advantages
In vitro Lyn kinase activity is increased.
In vivo reduction of glucose and weight gain is described in diabetic/obesity animal models.
In vivo reduced fat pad development is described in diabetic/obesity animal models.
Documented Applications
Treating gestational diabetes mellitus (GDM) or maturity onset diabetes of the young (MODY) in a mammal.
Treating or preventing Lyn kinase-associated metabolic syndrome (Syndrome X), dyslipidemia/dyslipoproteinemia, and glucose metabolism disorders including type II diabetes, gestational diabetes mellitus (GDM), and maturity onset diabetes of the young (MODY).
Treating or preventing obesity and cardiovascular disease.
Treating or preventing inflammation, septicemia, thrombotic disorders, renal diseases, pancreatitis, and hypertension.
Treating or preventing cancer and impotence.
Interested in licensing this patent?