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AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Pre-clinical testing demonstrates that the AGRO100 inhibition of nucleolin function produces anti-cancer effects against multiple types of the disease, including lung, prostate, breast, cervical, and colon cancer, as well as malignant melanoma and leukemia.
AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Pre-clinical testing demonstrates that the AGRO100 inhibition of nucleolin function produces anti-cancer effects against multiple types of the disease, including lung, prostate, breast, cervical, and colon cancer, as well as malignant melanoma and leukemia.
AGRO100, an experimental anticancer drug that recently entered human clinical trials, is a member of a novel class of antiproliferative agents known as G-rich oligonucleotides (GRO), which are non-antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G-quadruplex structures. The biological activity of GROs results from their binding to specific cellular proteins as aptamers. One important target protein of GROs has been previously identified as nucleolin, a multifunctional protein expressed at high levels by cancer cells. AGRO100 also associates with nuclear factor-{kappa}B (NF-{kappa}B) essential modulator (NEMO), which is a regulatory subunit of the inhibitor of {kappa}B (I{kappa}B) kinase (IKK) complex, and also called IKK{gamma}. In the classic NF-{kappa}B pathway, the IKK complex is required for phosphorylation of I{kappa}B{alpha} and subsequent activation of the transcription factor NF-{kappa}B. Research shows that treatment of cancer cells with AGRO100 inhibits IKK activity and reduces phosphorylation of I{kappa}B{alpha} in response to tumor necrosis factor-{alpha} stimulation. It also shows that AGRO100 blocks both tumor necrosis factor-{alpha}-induced and constitutive NF-{kappa}B activity in human cancer cell lines derived from cervical, prostate, breast, and lung carcinomas. In addition, in AGRO100-treated cancer cells, NEMO is coprecipitated by nucleolin, indicating that both proteins are present in the same complex. Studies suggest that abrogation of NF-{kappa}B activity may contribute to the anticancer effects of AGRO100 and that nucleolin may play a previously unknown role in regulating the NF-{kappa}B pathway. [PubMed: 16891465]
Investigated for use/treatment in cancer/tumors (unspecified), kidney cancer, leukemia (myeloid), and pancreatic cancer.
One entry per invention. Patent families filed in the US, EP, WO and CN offices.
