Methods and compositions for gamma-glutamyl cycle modulation
AssigneeCancer Research Technology Limited
InventorsDavid RUBIN, Eyal RUBIN
Life of this patent
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Abstract
The present disclosure provides pharmaceutical compositions comprising Gamma-glutamyl cycle inhibitors (GGCI) and certain pharmaceutically acceptable salts thereof, and methods of use.
Claims29
A compound represented by formula (I):
- or an ester, stereoisomers, geometric isomers, tautomers, optical isomer, and pharmaceutically acceptable salts thereof, wherein:
- R is independently selected from optionally substituted aryl, heteroaryl, para-methoxyphenyl, methyl carbonyl, 2,6-dimethyl-1,5-heptadienyl, 2,6-dimethyl-5-heptenyl, ortho-hydroxy phenyl, phenyl, and 3-aldehyde-propyl;
- R2 is independently selected from the group consisting of H, COOH;
- and esterified glucose or glucuronic acid
- R3 and R4 are independently selected from H, methyl or lower alkyl;
- S is independently selected from the group consisting of optionally substituted sulfur, selenium tellurium, or oxygen,
- providing that where R3 and R4 are H, R is not ortho-hydroxyphenyl.
A pharmaceutical composition comprising a compound, salt, crystal or polymorph in any one of claims 1-7, and a pharmaceutically acceptable excipient.
A composition for selectively treating tumor cells, comprising an effective amount of a 5-oxoproline analog, whereby the analog is metabolized and is effective in inhibiting the synthesis of glutamic acid in the gamma-glutamyl cycle.
A composition comprising a substantially pure GGCI crystal having alternating layers of GGCI molecules and besylate molecules (besylate salt).
The use of claim 15, whereby tumor progression is inhibited, or reduced, or MDR is inhibited or reduced.
A method of treating cancer comprising administering to a subject, in need thereof, a therapeutically effective amount of a pharmaceutical composition comprising a gamma-glutamyl cycle inhibitor (GGCI), whereby biosynthesis by the gamma-glutamyl cycle is inhibited.
The method of claim 34, wherein each dose of GGCI is between about 1 ng/kg and less than about 10 mg/kg, and said dose is administered by a delivery route selected from the group consisting of intradermal, intramuscular, intraperitoneal, intravenous, topical, subcutaneous, oral and epidural routes.
A compound represented by formula (I):
- or an ester, stereoisomers, geometric isomers, tautomers, optical isomer, and pharmaceutically acceptable salts thereof, wherein:
- R is independently selected from optionally substituted aryl, heteroaryl, para-methoxyphenyl, methyl carbonyl, 2,6-dimethyl-1,5-heptadienyl, 2,6-dimethyl-5-heptenyl, ortho-hydroxy phenyl, phenyl, and 3-aldehyde-propyl;
- R2 is independently selected from the group consisting of H, COOH;
- and esterified glucose or glucuronic acid
- R3 and R4 are independently selected from H, methyl or lower alkyl;
- with the proviso that wherein R3 and R4 are H, the aldehyde is not salicylaldehyde
- S is independently selected from the group consisting of optionally substituted sulfur, selenium tellurium, or oxygen.
Dependencies are inferred from the claim text.