Specific kinase inhibitors
OwnerDaniel Santi, Ralph Reid +3inventors
InventorsDaniel Santi, Ralph Reid, C. Hutchinson, Kurt Sundermann, Janice Lau
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Abstract
Resorcylic acid lactones having a C5-C6 cis double bond and a ketone at C7 and other compounds capable of Michael adduct formation are potent and stable inhibitors of a subset of protein kinases having a specific cysteine residue in the ATP binding site.
Claims74
A method for inhibiting one or more protein kinases in a mixture or cell, wherein said one or more protein kinases have a cysteine residue (Cys) located between two and immediately adjacent to one conserved aspartate residues in the ATP-binding site of said protein kinase, wherein said mixture comprises additional protein kinases lacking a Cys residue located between two and immediately adjacent to one conserved aspartate residues in an ATP-binding site of said additional protein kinases, said method comprising contacting said kinase with a compound capable of forming a Michael adduct with said Cys residue in said one or more protein kinases under conditions such that said Michael adduct forms between said compound and said Cys residue and results in inhibition of said one or more protein kinases.
A method for treating a disease or disease condition by administering to a patient in need of treatment for said disease or disease condition a pharmaceutical composition that comprises a compound that specifically inhibits a protein kinase having a cysteine residue (Cys) located between and immediately adjacent to one of two conserved aspartate residues in the ATP-binding site region of said protein kinase, said method comprising contacting said kinase with a compound that forms a Michael adduct with said Cys.
A purified and isolated compound having a structure according to formula II:
A method for preparing a compound having a structure according to formula II
- comprising the step of culturing the organism Hypomyces subiculosus DSM 11931 in a culture medium containing D,L-ethionine in an amount of between about 10 and about 100 mg/L of culture medium.
Dependencies are inferred from the claim text.