Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2007-08-21
2007-08-21
Lukton, David (Department: 1654)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C560S008000, C562S405000
Reexamination Certificate
active
09725030
ABSTRACT:
It is presently accepted that the mechanism of action for all anti-tumor tubulin ligands involves the perturbation of microtubule dynamics during the G2/M phase of cell division and subsequent entry into apoptosis (1). In this invention, we report a novel tubulin ligands which have a unique mechanism of action. These compounds, halogenated derivatives of acetamido benzoyl ethyl ester (HAABE), arrest cancer cells in S-phase and cause cell death by a combination of apoptosis (DNA ladder) and necrosis (DNA degradation) type mechanisms. Normal cells are not affected at the same concentrations of compound. The ligands bind covalently to tubulin in vitro and in vivo and shows potent cancericidal activity in tissue culture assays and in animal tumor models. These compounds target early S-phase at the G1/S transition rather than the G2/M phase and mitotic arrest. Bcl-2 phosphorylation, a marker of mitotic microtubule inhibition by other tubulin ligands was dramatically altered, phosphorylation was rapid and biphasic rather than a slow linear event. The halogenated ethyl ester series of derivatives thus constitute a unique set of tubulin ligands which induce a novel mechanism of cancer cell death.
REFERENCES:
Jiang Cancer Research 58, 2126, 1998.
Jiang J D, Cancer Research 58 (23) 5389□95, 1998.
Alberts The Molecular Biology of the Cell, 2nd Ed., 1989, pp. 727-786.
Abraham I., Proc Natl. Acad. Sci. 83, 6839-43, 1986.
Sorger P.K., Curr Opin Cell Biol. 9, 807-814, 1997.
Jordan, Current Opinion in Cell Biology 10 (1) 123-30, 1998.
Fang X. (Biochemical Journal 352 Pt 1 135 42, 2000).
Steiner M. R. (Annals of the New York Academy of Sciences 95 132 41, 2000).
Tsuchiyama Y (Kidney International 58 (5) 1941-52, 2000).
Urbani C., Tropical medicine & international health : TM & IH, (Nov. 2001) 6 (11) 935-44.
Kerboeuf Dominique, International journal of antimicrobial agents, (Sep. 2003.) 22 (3) 332-46.
Wolstenholme Adrian J., Trends in parasitology, (Oct. 2004) 20 (10) 469-76.
Miljutin, D. M., Nematology, (2001) vol. 3, No. 6, pp. 491-502.
A. Davis et al. Novel suicide ligands of tubulin arrest cancer cells in S-phase. Neoplasia, 1 (6), p. 498-507. 1999.
Jaing J.D. et al. Synthesis, cancericidal and anti-microtubule activities of 3-haloacetamido-benzoyl-ureas. Anti-Cancer Drug Design, 13 (7), p. 735-747. 1998.
Bekesi J. George
Davis Ashley Stuart
Jiang Jain Dong
Middleton Kim Maria
Cozen O'Connor P.C.
Cytoskeleton Inc.
Lukton David
LandOfFree
Anti-S-phase tubulin ligands does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anti-S-phase tubulin ligands, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anti-S-phase tubulin ligands will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3849877