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AssigneeAlbany Medical College
InventorsThomas T. Andersen, James A. Bennett, Herbert I. Jacobson, Fassil B. Mesfin
Estimating the term…
Therapeutic compounds which are cell proliferation modulators, preferably inhibitors. These modulators contain amino acid structures that are arranged as a hydrophilic analog of an alpha-fetoprotein. The modulator may be a peptide itself, e.g., an octapeptide like that of SEQ ID NO: 5; a peptidomimetic; or may be in the form of a pharmaceutically acceptable scaffold, such as a polycyclic hydrocarbon to which is attached the necessary amino acid structures for biological and/or chemical activity. The modulators of the invention are distinguished in one aspect over previous compounds in that they are orally active, and therefore do not have to be injected into the patient. The compositions and methods are useful for reducing estrogen-dependent and estrogen-independent growth of cells, and treating or preventing cancer, such as breast cancer, brain cancer, head-and-neck cancer, thyroid cancer, lung cancer, colon cancer, ovarian cancer, prostate cancer, cervical cancer, and skin cancer. The treatment or prevention methods can include the use of tamoxifen therapy in combination with the peptide therapy.
A method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of an alpha-fetoprotein peptide selected from the group consisting of the amino acid sequence of EKTOVNOGN (SEQ ID NO:1) and EKTOVNOGN (SEQ ID NO:1) wherein the lysine residue is D-lysine or acetylated L-lysine, wherein said peptide modulates cell proliferation such that cancer is treated.
A method of blocking or inhibiting ER phosphorylation, comprising adding to a system containing ER an alpha-fetoprotein peptide selected from the group consisting of the amino acid sequence of EKTOVNOGN (SEQ ID NO:1) and EKTOVNOGN (SEQ ID NO:1) wherein the lysine residue is D-lysine or acetylated L-lysine, such that the AFP peptide blocks or inhibits ER phosphorylation.
A method of modulating an interaction between MAPK and ER, comprising adding to a system containing MAPK and ER, an agent that modulates ER phosphorylation by mitogen-activated protein kinase (MAPK), such that an interaction between MAPK and ER is modulated, wherein the agent is an alpha-fetoprotein peptide selected from the group consisting of the amino acid sequence of EKTOVNOGN (SEQ ID NO:1) and EKTOVNOGN (SEQ ID NO:1) wherein the lysine residue is D-lysine or acetylated L-lysine.
A method of modulating E2 activation of ER, comprising adding, to a system containing MAPK and ER, an agent that modulates ER phosphorylation by MAPK, such that E2 activation of ER is modulated, wherein the agent is an alpha-fetoprotein peptide selected from the group consisting of the amino acid sequence of EKTOVNOGN (SEQ ID NO:1) and EKTOVNOGN (SEQ ID NO:1) wherein the lysine residue is D-lysine or acetylated L-lysine.
Dependencies are inferred from the claim text.