Pharmaceutical compounds
Inventors
Shorr, Robert • Rodriguez, Robert • BINGHAM, PAUL • Boteju, Lakmal • Kwok, Thomas • Marecek, James
Assignees
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Publication Number
US-10179796-B2
Publication Date
2019-01-15
Expiration Date
Abstract
Therapeutically-effective amounts of novel analogs or derivatives of alkyl fatty acids, such as but not limited to lipoic acid, and pharmaceutical formulations comprising such analogs or derivatives and pharmaceutically-acceptable carriers therefor, are useful for the treatment, prevention, imaging, and/or diagnosis of medical disorders.
Core Innovation
The invention provides alkyl fatty acid analogs/derivatives, including lipoic acid (6,8-dithiooctanoic acid), having defined general chemical structures with variable substituent groups (R1–R5 and chain-length related variables such as n and x). The disclosed scope includes specific structural alternatives for the analogs, and it also includes pharmaceutically acceptable salts and prodrugs/solvates.
The invention further provides pharmaceutical formulations comprising at least one alkyl fatty acid analog and at least one pharmaceutically acceptable carrier/excipient. The disclosed use includes treatment, prevention, and imaging/diagnosis of warm-blooded animal diseases, where utility is tied to selective targeting of altered mitochondrial PDH complex activity and α-KDH, ADH, and BCKADH complex activity in disease states.
The disclosed disease utility is directed to hyperproliferative/Warburg-associated disease states, including cancer and non-cancer disease categories. Cancer examples explicitly include melanoma (primary and metastatic), lung, liver, Hodgkin/non-Hodgkin lymphoma, uterine, cervical, bladder, kidney, colon, breast, prostate, ovarian, pancreatic cancers, and sarcoma, while non-cancer examples include age-related macular degeneration, Crohn’s disease, cirrhosis, diabetic retinopathy/neuropathy, rheumatoid arthritis, and systemic lupus erythematosus.
Claims Coverage
The provided independent claims cover alkyl fatty acid analogs defined by structure, pharmaceutical formulations including pharmaceutically acceptable carriers, and therapeutic methods by administering therapeutically effective amounts for a defined set of cancers/lymphomas. Across the independent claims, the inventive features include: selecting an alkyl fatty acid analog from defined alternatives or from a defined general chemical formula; using the analog in formulations with pharmaceutically acceptable carriers; and treating enumerated cancer/lymphoma diseases via administration to a patient.
Alkyl fatty acid analog selected from specified alternatives
Selecting an alkyl fatty acid analog selected from the group consisting of the specified alternatives, with refinements to particular depicted chemical structures and/or defined analogs via embedded structures/images.
Alkyl fatty acid analog or pharmaceutically acceptable salt thereof
Providing an alkyl fatty acid analog selected from the specified set, or a pharmaceutically acceptable salt thereof, with refinements to particular chemical structures shown in embedded images and salt forms.
Alkyl fatty acid analog defined by general formula constraints
An alkyl fatty acid analog having the general formula where n is 2, x is 1–16, R1 and R2 are independently alkylaryl or alkylheteroaryl, and R5 is unsubstituted alkyl, a phosphonium, a phosphonate, or a sulfonic acid, or a salt thereof.
Pharmaceutical formulation with a pharmaceutically acceptable carrier
A pharmaceutical formulation including at least one alkyl fatty acid analog together with at least one pharmaceutically acceptable carrier.
Treating cancers and lymphomas by administering a therapeutically effective amount
Treating a selected set of cancers and lymphomas by administering to a patient a therapeutically effective amount of at least one alkyl fatty acid analog as specified in the earlier claim.
Therapeutic use for lung cancer, pancreatic cancer, or sarcoma
The treating method is applied to lung cancer, pancreatic cancer, or a sarcoma.
Overall, the independent claims define specific alkyl fatty acid analogs by selected alternatives or by a constrained general formula, include pharmaceutically acceptable salts, require formulation with pharmaceutically acceptable carriers, and claim therapeutic treatment of enumerated cancers/lymphomas by administering a therapeutically effective amount, with further narrowing to lung cancer, pancreatic cancer, or sarcoma.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of warm-blooded animal diseases via selective targeting of altered mitochondrial PDH complex activity and α-KDH, ADH, and BCKADH complex activity in Warburg-associated hyperproliferative disease states.
Prevention of diseases in warm-blooded animals.
Imaging/diagnosis of diseases in warm-blooded animals.
In vitro testing for cell-killing activity against BXPC3, H460, and SF539 cell lines with reported percent viable cells at 50 μM and 100 μM.
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