CA IX-specific inhibitors

Details CA IX-specific inhibitors CA IX-specific inhibitors

2007-10-30

2010-11-16

Fetterolf, Brandon J (Department: 1642)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

Reexamination Certificate

active

07833737

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 organic compounds, preferably aromatic and heterocylic sulfonamides, which inhibit the enzymatic activity of MN/CA IX and that are useful for treating patients with preneoplastic
eoplastic disease. Further, the CA IX-specific inhibitors when labeled or linked to an appropriate visualizing means can also be used diagnostically/prognostically for preneoplastic
eoplastic disease, and for imaging use, for example, to detect hypoxic precancerous cells, tumors and/or metastases, by selectively binding to activated CA IX, preferably CA IX activated under hypoxic conditions, and not to inactive CA IX. Such detection of hypoxic conditions can be helpful in determining effective treatment options, and in predicting treatment outcome and the prognosis of disease development. Still further, the CA IX-specific inhibitors can be used therapeutically to selectively target hypoxic cells expressing activated CA IX. The CA IX-specific inhibitors can be labeled or conjugated to radioisotopes for radiotherapy of hypoxic cells. Alternatively, the CA IX-specific inhibitors can be used for gene therapy coupled to vectors for targeted delivery to hypoxic preneoplastic
eoplastic cells expressing activated CA IX on their surfaces. In an alternative mode of the invention, CA IX-specific inhibitors may be used therapeutically to target acidic conditions of a tumor, e.g., to increase pHe in order to enhance the efficacy of weak base chemotherapeutic drugs.

REFERENCES:
patent: 5610304 (1997-03-01), Yoshino et al.
patent: 6034099 (2000-03-01), Pamukeu et al.
patent: 6284923 (2001-09-01), Medina et al.
Dorwald F. A. (Side reactions in organic synthesis, 2005, Wiley, VCH, Weinheim, p. IX of Preface).
Casey et al., “Carbonic Anhydrase Inhibitors. Design of Selective, Membrane-Impermeant Inhibitors Targeting the Human Tumor-Associated Isozyme IX,”J. Med Chem., 47: 2337-2347 (2004).
Gerweck, L.E., “Tumor pH: Implications for Treatment and Novel Drug Design,”Seminars in Radiation Oncology, 8(3): 176-182 (Jul. 1998).
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 inhibitors. 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 Lipophillic Sulfonamides,”Journal of Enzyme Inhibition and Medicinal Chemistry, 18(4): 333-338 (Aug. 2003).
Hies 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 witha 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., 292-300 (Jan. 27, 2000).
Sterling et al., “The functional anti physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II,”Am. J. Physiol. Cell Phsiol., 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-thladizole- 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).
Winnum et al., “Carbonic Anhydrase Inhibitors. Inhibition of Cytosolic Isozymes I and II and Transmembrane, Tumor-Associated Isozyme IX with Sulfamates Including EMATE Also Acting as Steroid Sulfatase Inhibitors,”J. Med. Chem., 46(11): 2197-2204 (May 22, 2003).
Wistrand and Lindqvist, “Design of Carbonic Anhydrase Inhibitors and the Relationship Between the Pharmacodynamics and Pharmacokinetics of Acetazolamide,”In Carbonic Anhydrase—From Biochemistry and Genetics to Physiology and Clinical Medicine, Bo

Affiliated with

Also associated with

Rating

CA IX-specific inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with CA IX-specific inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and CA IX-specific inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4251673