Inducible phosphofructokinase and the warburg effect
OwnerRichard J. Bucala, Jason A. Chesney +1inventors
InventorsRichard J. Bucala, Jason A. Chesney, Robert A. Mitchell
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Abstract
There is disclosed a cancer malignancy diagnostic assay comprising obtaining a sample of a body fluid or tissue, performing a sequence identity assay to look for the presence of iPFK-2 specific sequences; an anticancer pharmaceutical composition comprising a specific antisense oligonucleotide to the inventive isolated iPFK-2 sequence and a pharmaceutically acceptable oligonucleotide carrier; and a method for finding therapeutically active anti-cancer compounds comprising screening compounds for activity to inhibit iPFK-2, preferably kinase activity.
Claims17
A cancer malignancy diagnostic assay comprising obtaining a sample of a body or tumor fluid or tissue, performing a sequence identity assay to look for the presence of iPFK-2 specific sequences.
An anticancer pharmaceutical composition comprising a specific antisense oligonucleotide of at least 10 bases complimentary to the iPFK-2 cDNA sequence [SEQ ID NO. 11] and a pharmaceutically acceptable oligonucleotide carrier.
A method for screening for anticancer therapeutic agents that inhibit kinase enzymatic activity of iPFK-2, comprising:
- (a) expressing an iPFK-2 enzyme or kinase domain thereof from the cDNA sequence of SEQ ID NO. 11;
- (b) purifying and isolating the expressed iPFK-2 enzyme or kinase domain thereof;
- (c) providing a candidate therapeutic agent and fructose 6-phosphate substrate;
- and
- (d) measuring formation of fructose 2,6-bisphosphate product as a measure of kinase enzymatic activity.
An antibody that binds to an epitope of iPFK-2, wherein the epitope comprises a sequence of amino acids corresponding to amino acids 505-515 of iPFK-2.
An isolated DNA sequence encoding an iPFK-2 polypeptide and comprising a coding region of the sequence described in SEQ ID NO.:
- 11.
An isolated iPFK-2 polypeptide expressed by the cDNA sequence described in SEQ ID NO.:
- 11.
An isolated DNA sequence encoding a kinase domain of an iPFK-2 polpeptide comprising base pairs 47-797 of SEQ ID NO. 11.
An isolated iPFK-2 kinase domain polypeptide expressed by base pairs 47-797 of SEQ ID NO. 11.
An anti-inflammatory pharmaceutical composition comprising a specific antisense oligonucleotide of at least 10 bases complimentary to an iPFK-2 cDNA sequence [SEQ ID NO. 11] and a pharmaceutically acceptable oligonucleotide carrier.
A method for treating inflammatory diseases, comprising administering an effective amount of an iPFK-2 antagonist.
A method for treating cancers, comprising administering an effective amount of an iPFK-2 antagonist.
Dependencies are inferred from the claim text.