Programmable genotoxic agents and uses therefor

Details Programmable genotoxic agents and uses therefor Programmable genotoxic agents and uses therefor

2007-01-30

2007-01-30

Riley, Jezia (Department: 1637)

Chemistry: molecular biology and microbiology

Process of mutation, cell fusion, or genetic modification

Mutation employing a chemical mutagenic agent

C435S004000, C435S006120, C435S007100, C435S007200, C536S023100, C552S502000

Reexamination Certificate

active

10299029

ABSTRACT:
The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.

REFERENCES:
patent: 3299104 (1967-01-01), Fex et al.
patent: 5354745 (1994-10-01), Tamura et al.
patent: 5879917 (1999-03-01), Essigmann et al.
patent: 5882941 (1999-03-01), Essigmann et al.
patent: 6500669 (2002-12-01), Essigmann et al.
patent: 1 265 811 (1990-02-01), None
patent: 0 208 446 (1986-06-01), None
patent: WO91/08743 (1990-12-01), None
patent: WO 92/14843 (1992-03-01), None
Nobori et al. (1994), Deletions of the Cyclin-Dependent Kinase-4 Inhibitor Gene in Multiple Human Cancers,: 368Nature753-756.
Xiong et al. (1993), “Subunit Rearrangement of the Cyclin-Dependent Kinases is Associated with Cellular Transformation,” 7Genes&Dev., 1572-1583.
Keyomarsi et al. (1993), “Redundant Cyclin Overexpression and Gene Amplification in Breast Cancer Cells,” 90Proc. Nat'l. Acad. Sci., USA1112-1116.
Stephen et al. (1992), “Mutant Conformation of p53,” 225J. Mol. Biol. 577-583.
Hollstein et al. (1991), “p53 Mutations in-Human Cancers,” 253Science49-53.
Marx (1990), “Genetic Defect Identified in Rare Cancer Syndrome,” 250Science1209.
Malkin et al. (1990), “Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms,” 250Science1233-1238.
Vogelstein (1990), “A Deadly Inheritance,” 348Nature681-682.
Srivastava et al. (1990), “Germ-Line Transmission of a Mutated p53 Gene in a Cancer-prone Family wtih Li-Fraumeni Syndrome,” 348Nature747-749.
Gannon et al. (1990), “Activating Mutations in p53 Produce a Common Conformational Effect. A Monoclonal Antibody Specific For The Mutant Form,” 9EMBO J. 5:1595-1602.
Muntzing et al. (1972), “Lipofuscin in Malignant and Non-Malignant Human Prostatic Tissue,” 77Z. Krebsforsch166-170.
Nieulescu-Duvaz et al. (1966), “Potential Anticancer Agents II Urethan Type Nitrogen Mustards of Some Natural Sex Hormones,” 10J. Med. Chem. 172-174.
Holley et al. (1992), “Targeting of Tumor Cells and DNA by a Chlorambucil-Spermidine Conjugate,” 52Cancer Res. 4190-4195.
Kosano et al. (1992), “Growth-Inhibitory Action of An Estrogen-Chloramucil Conjugate (KM2210) in Human Breast Cancer Cell Line MCF-7: Its Relationship to Reduction of Estrogen Receptor and Transforming Growth Factor-α Section,” 52Cancer Res. 1187-1191.
Otto et al. (1991), “Dissociation of Estrogenic and Cytotoxic Properties of an Estrogen Receptor-Binding Platinum Complex in Human Breast Cancer Cell Lines,” 51Cancer Res. 3217-3223.
Knebel and von Angerer (1991), “2-Phenylindole-Linked [2-(Aminoalkyl) pyridine] dichloroplatinum(II): Complexes With A Selective Action on Estrogen Receptor Positive Mammary Tumors,” 34J. Med. Chem7:2145-2152.
von Angerer et al. (1984), “2Phenylindoles—Relationship Between Structure, Estrogen Receptor Affinity, and Mammary Tumor Inhibiting Activity in the Rat,” 27J. Med. Chem. 1439-1447.
Georgiadis et al. (1987), “Synthesis and Biological Studies Steroidal cis-Platinum(II) Complexes,” 138Inorg. Chim. Acta249-252.
Wakeling and Bowler (1988), “Novel Antioestrogens Without Partial Agonist Activity,” 31J. Steroid Biochem. No. 4B:645-653.
Jones et al. (1984) “Antiestrogens 2. Structure-Activity Studies in a Series of 3-Aroyl-2-arylbenzo[b]thiophene Derivatives Leading to [6-Hydroxy-2-(4-hydroxyphenyl)benzol[b]thien-3-yl][4-[2-(1-piperdinyl)ethyoxy]-phenyl]methanone Hydrochloride (LY156768), a Remarkable Effective Estrogen Antagonist With Only Minimal Intrinsic Estrogenicity,” 27J. Med. Chem. 1057-1066.
Leclercq et al. (1983), “Guide-Lines in the Design of New Antiestrogens and Cytotoxic-Linked Estrogens For The Treatment of Breast Cancer,” 19J. Steroid Biochem. 75-85.
Katzenellenbogen et al. (1980), “The Chemistry of Estrogens and Antiestrogens: Relationships Between Structure, Receptor Binding, and Biological Activity,”Estrogens in the Environment(Mclachlan, ed.) 33-51.
Jordan et al. (1980), “Structural Derivatives of Tamifoxen and Oestradiol 3-methyl Ether as Potential Alkylating Antioestrogens,” 17Eur. J. Cancer193-201.
Redeuilh et al. (1980), “Properties of Biospecific Absorbents Obtained by Immobilization of Oestradiol 7 Derivatives, For Purification of Calf-Uterine Cytosol Oestradiol Receptor,” 106Eur. J. Biochem. 481-493.
Jones et al. (1993), “Preferential Binding of the Xeroderma Pigmentosum Group A Complementing Protein to Damaged DNA,” 32Biochem. 12096-12104.
Batist et al. (1989), “Enhanced DNA Cross-Link Removal: The Apparent Mechanism of Resistance in a Clinically Relevant Melphalan-Resistant Human Breast Cancer Cell Line,” 36Mol. Pharmacol. 224-230.
Devchand et al. (1993), “Uracil-DNA Glycosylase As A Probe For Protein-DNA Interactions,” 21Nucl. Acids Res. 15:3437-3443.
Sibghat-Ullah and Sancar (1990), “Substrate Overlap and Functional Competition Between Human Nucleotide Excision Repair andEscherichia coliPhotolyase and (A)BC Excision Nuclease,” 29Biochem. 5711-5718.
Lippard (1994), “Structural and Biological Consequences of Platinum Anticancer Drug Binding to DNA,” Chapter 4 ofProceedings of The Robert A. Welch Foundation 37th Conference on Chemical Research, 40 Years of the DNA Double Helix, Oct. 25-26, 1993, The Westin Oaks Hotel, Houston, Texas (1994).
Bruhn et al. (1993), “Isolation and Characterization of cDNA Clones Encoding theDrosophilaHomolog of the HMG-Box SSRP-Family That Recognized Specific DNA Structures,” 21Nucl. Acids Res. 1643-1646.
Bradley et al. (1993), “Mutagenicity and Genotoxicity of the Major DNA Adduct of the Anti-Tumor Druge cis-Diamminedichloroplatinum(II),” 32Biochem. 982-988.
Brown et al. (1993), “Ixr1, a Yeast Protein That Binds to Platinated DNA and Confers Sensitivity to Cisplatin,” 261Science603-605.
Weir et al. (1993), “Structure of the HMG Box Motif in the B-Domain of HMG1,” 12EMBO J, 4:1311-1319.
Pil et al. (1993), “High-Mobility Group 1 Protein Mediates DNA Bending as Determined by Ring Closures,” 90Proc. Nat'l. Acad. Sci. USA9465-9469.
Dabholkar et al. (1992), “Determinants of Cisplatin Sensitivity in Non-Malignant Non-Drug Selected Human T Cells,” 274Mut. Res. 45-56.
Treiber et al. (1992), “An Ultraviolet Light-Damaged DNA Recognition Protein Absent in Xeroderma Pigmentosum Group E Cells Binds Selectively to Pyrimidine (6-4) Pyrimidome Photoproducts,” 20Nucl. Acids Res. 21:5805-5810.
Szymkowski et al. (1992), “An Intrastrand d(GpG) Platinum Crosslink in Duplex M13 DNA is Refractory to Repair by Human Cell Extracts,” 89Proc. Nat'l. Acad. Sci. USA10772-10776.
Zhen et al. (1992), “Increased Gene-Specific Repair of Cisplatin Interstrand Cross-Links in Cisplatin-Resistant Human Ovarian Cancer Cell Lines,” 12Mol. Cell. Biol.9:3689-3698.
Hughes et al. (1992), “Purification of Nuclear Proteins That Bind to Cisplatin-Damaged DNA,” 267J. Biol. Chem.13520-13527.
Pil et al. (1992), “Specific Binding of Chromosomal Protein HMG 1 to D

Affiliated with

Also associated with

Rating

Programmable genotoxic agents and uses therefor does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Programmable genotoxic agents and uses therefor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Programmable genotoxic agents and uses therefor will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3738587