CA IX-specific inhibitors

Details CA IX-specific inhibitors CA IX-specific inhibitors

2003-11-26

2009-06-23

Fetterolf, Brandon J (Department: 1642)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C435S004000

Reexamination Certificate

active

07550424

ABSTRACT:
Therapeutic methods for inhibiting the growth of preneoplastic
eoplastic vertebrate cells that abnormally express MN protein are disclosed. Screening assays are provided for identifying compounds, preferably membrane-impermeant compounds, which inhibit the enzymatic activity of MN protein/polypeptides and that are useful for treating patients with preneoplastic
eoplastic disease. Further methods are disclosed for the preparation of positively-charged, membrane-impermeant heterocyclic sulfonamide CA inhibitors with high affinity for the membrane-bound carbonic anhydrase CA IX. Preferred CA IX-specific inhibitors are aromatic and heterocylic sulfonamides, preferably that are membrane-impermeant. Particularly preferred CA IX-specific inhibitors are pyridinium derivatives of such aromatic and heterocyclic sulfonamides. The CA IX-specific inhibitors of the invention can also be used diagnostically/prognostically for preneoplastic
eoplastic disease, and for imaging use, for example, to detect precancerous cells, tumors and/or metastases. The CA IX-specific inhibitors can be labelled or conjugated to radioisotopes for radiotherapy. The CA IX-specific inhibitors may be combined with conventional therapeutic anti-cancer drugs, with other different inhibitors of cancer-related pathways, with bioreductive drugs, or with radiotherapy to enhance the efficiency of each treatment. The CA IX-specific inhibitors may also be combined with CA IX-specific antibodies, preferably monoclonal antibodies or biologically active antibody fragments, more preferably humanized or fully human CA IX monoclonal antibodies or biologically active fragments or such monoclonal antibodies. Still further, the CA IX-specific inhibitors can be used for gene therapy coupled to vectors for targeted delivery to preneoplastic
eoplastic cells expressing CA IX on their surfaces.

REFERENCES:
patent: 6027887 (2000-02-01), Zavada et al.
patent: 6034099 (2000-03-01), Pamukcu et al.
Sigma® Product Information for Fluoresceine Isothiocynate (Dec. 2000).
Loncaster et al. (Cancer Research 2001; 61: 6394-6399).
Parkkila et al. (PNAS 2000; 97: 2220-2224).
Parkkila et al. (Histochemical Journal 1995; 27: 974-982).
Supuran et al. (Expert Opinion on Therapeutic Patents 2000; 10: 575-600).
Supuran et al. (Curr. Med. Chem.-Imm., Endoc. & Metab. Agents 2001; 1: 61-97).
Casini et al., “Carbonic Anhydrase Inhibitors: Water-Soluble 4-Sulfamoylphenylthioureas as Topical Intraocular Pressure-Lowering Agents with Long-Lasting Effects,”J. Med. Chem., 43: 4884-4892 (2000).
Chegwidden et al., “The Roles of Carbonic Anhydrase Isozymes in Cancer,”Gene Families: Studies of DNA, RNA, Enzymes and Proteins, Proceedings of the International Isozymes, 10th, Beijing, China, Oct. 5-10, 1999, Meeting Date 1999, 157-169 (Xue, G. ed.; World Scientific Pub. Co.; 2001).
Clare and Supuran, “Carbonic anhydrase iinhibitors. Part 61. Quantum chemical QSAR of a group of benzenedisulfonamides,”Eur. J. Med. Chem., 34: 463-474 (1999).
Cuthbert et al., “Bicarbonate-dependent chloride secretion in Calu-3 epithelia in response to 7,8-benzoquinoline,”J Physiol., 551 (Pt 1): 79-92 (Aug. 15, 2003).
Franchi et al., “Carbonic Anhydrase Inhibitors. Inhibition of Cytosolic Isozymes I and II and Transmembrane, Cancer-associated Isozyme IX with Lipophilic Sulfonamides,”Journal of Enzyme Inhibition and Medicinal Chemistry, 18(4): 333-338 (Aug. 2003).
Ilies et al., “Carbonic Anhydrase Inhibitors. Inhibition of Tumor-Associated Isozyme IX by Halogenosulfanilamide and Halogenophenylaminobenzolamide Derivatives,”J. Med. Chem., 46: 2187-2196 (2003).
Pastorek et al., “Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment,”Oncogene, 9: 2877-2888 (1994).
Scozzafava and Supuran, “Carbonic Anhydrase Inhibitors: Synthesis ofN-Morpholylthiocarbonylsulfenylamino Aromatic/Heterocyclic Sulfonamides and their Interaction with Isozymes I, II and IV,”Bioorganic&Medicinal Chemistry Letters, 10: 1117-1120 (2000).
Scozzafava et al., “Carbonic Anhydrase Inhibitors. Synthesis of Water-Soluble, Topically Effective, Intraocular Pressure-Lowering Aromatic/Heterocyclic Sulfonamides Containing Cationic or Anionic Moieties: Is the Tail More Important than the Ring?”J. Med. Chem., 42: 2641-2650 (1999).
Scozzafava et al., “Carbonic Anhydrase Inhibitors: Synthesis of Membrane-Impermeant Low Molecular Weight Sulfonamides Possessing in Vivo Selectivity for the Membrane-Bound versus Cytosolic Isozymes,”J. Med. Chem., 43: 292-300 (Jan. 27, 2000).
Sterling et al., “The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II,”Am. J. Physiol. Cell Physiol., 283(5): C1522-C1529 (Nov. 2002).
Supuran and Clare, “Carbonic anhydrase inhibitors. Part 24. A quantitative structure-activity relationship study of positively charged sulfonamide inhibitors,”Eur. J. Med. Chem., 30: 687-696 (1995).
Supuran and Clare, “Carbonic anhydrase inhibitors—Part 57: Quantum chemical QSAR of a group of 1,3,4-thiadiazole- and 1,3,4-thiadiazoline disulfonamides with carbonic anhydrase inhibitory properties,”Eur. J. Med. Chem., 34: 41-50 (1999).
Supuran and Scozzafava, “Carbonic Anhydrase Inhibitors: Aromatic Sulfonamides and Disulfonamides Act as Efficient Tumor Growth Inhibitors,”J. Enzyme Inhib., 15(6): 597-610 (2000).
Supuran and Scozzafava, “Carbonic anhydrase inhibitors—Part 94. 1,3,4-Thiadiazole-2-sulfonamide derivatives as antitumor agents?,”Eur. J. Med. Chem., 35(9):867-874 (Sep. 2000).
Supuran et al., “Carbonic anhydrase inhibitors—Part 53. Synthesis of substituted-pyridinium derivatives of aromatic sulfonamides: The first non-polymeric membrane-impermeable inhibitors with selectivity for isozyme IV,”Eur. J. Med. Chem., 33: 577-594 (1998).
Supuran et al., “Carbonic anhydrase inhibitors—Part 29: Interaction of isozymes I, II and IV with benzolamide-like derivatives,”Eur. J. Med. Chem., 33: 739-751 (1998).
Supuran et al., “Carbonic Anhydrase Inhibitors: Synthesis of Sulfonamides Incorporating 2,4,6-Trisubstituted-Pyridinium-Ethylcarboxamido Moieties Possessing Membrane-Impermeability and In Vivo Selectivity for the Membrane-Bound (CA IV) Versus the Cytosolic (CA I and CA II) Isozymes,”J. Enzyme Inhibition, 15(4): 381-401 (2000).
Supuran et al., “Carbonic Anhydrase Inhibitors: Sulfonamides as Antitumor Agents?,”Bioorganic&Medicinal Chemistry, 9(3): 703-714 (Mar. 2001).
Supuran et al., “Carbonic Anhydrase Inhibitors,”Medicinal Research Reviews, 23(2): 146-189 (Mar. 2003).
Teicher et al., “A Carbonic Anhydrase Inhibitor as a Potential Modulator of Cancer Therapies,”Anticancer Research, 13: 1549-1556 (1993).
Vullo et al., “Carbonic Anhydrase Inhibitors. Inhibition of Cytosolic Isozymes I and II and Transmembrane, Cancer-associated Isozyme IX with Anions,”Journal of Enzyme Inhibition and Medicinal Chemistry, 18(5): 403-406 (Oct. 2003).
Vullo et al., “Carbonic Anhydrase Inhibitors: Inhibition of the Tumor-Associated Isozyme IX with Aromatic and Heterocyclic Sulfonamides,”Bioorganic Medicinal Chemistry Letters, 13(6): 1005-1009 (Mar. 24, 2003).
Wingo et al., “The Catalytic Properties of Human Carbonic Anhydrase IX,”Biochemical and Biophysical Research Communications, 288: 666-669 (2001).
Anderson et al., “The Process of Structure-Based drug Design,”Chemistry&Biology, 10: 787-797 (Sep. 2003).
Knight et al., “Features of Selective Kinase Inhibitors,”Chemistry&Biology, 12: 621-631 (Jun. 2005).
Riendeau et al., “Etoricoxib (MK-0663): Preclinical Profile and Comparison with Other Agents That Selectively Inhibit Cyclooxygenase-2,”The Journal of Pharmacology and E

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