Patents Assigned to The Arizona Disease Control Research Commission
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Patent number: 7019031Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.Type: GrantFiled: October 23, 2001Date of Patent: March 28, 2006Assignee: The Arizona Disease Control Research CommissionInventors: Seth D. Rose, Scott R. Lefler, Steven R. Ottersberg, Ann Y. Kim, Karl J. Okolotowicz, Rosemarie F. Hartman
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Patent number: 7012097Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. ?-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.Type: GrantFiled: May 14, 2003Date of Patent: March 14, 2006Assignee: The Arizona Disease Control Research CommissionInventors: Seth D. Rose, Steven R. Ottersberg, Karl J. Okolotowicz, Dale E. Robinson, Rosemarie Hartman, Scott Lefler
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Publication number: 20060030624Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. ?-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.Type: ApplicationFiled: October 11, 2005Publication date: February 9, 2006Applicant: Arizona Disease Control Research CommissionInventors: Seth Rose, Steven Ottersberg, Karl Okolotowicz, Dale Robinson, Rosemarie Hartman, Scott Lefler
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Publication number: 20050026812Abstract: Conjugated nitro alkene compounds hamper or prevent proliferation of cancer cells in cell culture and in cancer patients, which can result in a decrease in tumor size and/or disappearance of the cancer. The compounds may act by interference with cancer cell biochemistry, in which isoprenoid groups such as farnesyl and geranylgeranyl become bonded to various oncogenic proteins such as Ras, RhoA, RhoB, or some other growth-related cellular protein(s).Type: ApplicationFiled: July 29, 2004Publication date: February 3, 2005Applicant: Arizona Disease Control Research CommissionInventors: Seth Rose, Karl Okolotowicz, Rosemarie Hartman, Jason Houtchens
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Patent number: 6812365Abstract: The present invention provides novel disulfone compounds and methods of preparing and using those compounds to further prepare biologically relevant gem-disulfone analogs of natural enzyme substrates. Methods of using a variety of disulfone compounds as reagents capable of forming symmetrical and non-symmetrical &agr;, &bgr; unsaturated gem-disulfones are also provided. There is also provided a disulfone reagent which reacts with both aromatic and aliphatic aldehydes in good to moderate yield to give exclusively the trans isomer. In accordance with further aspects of the present invention, a methodology for stereospecifically preparing potential gem-disulfone enzyme inhibitors is provided. A synthetic design which allows easy substitution of functional groups so that a number of substrate analogs can be synthesized readily is also provided.Type: GrantFiled: November 5, 2002Date of Patent: November 2, 2004Assignee: The Arizona Disease Control Research CommissionInventors: Jacqueline Gervay-Hague, Michael J. Hadd
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Publication number: 20030219847Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. &agr;-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.Type: ApplicationFiled: May 14, 2003Publication date: November 27, 2003Applicant: The Arizona Disease Control Research CommissionInventors: Seth D. Rose, Steven R. Ottersberg, Karl J. Okolotowicz, Dale E. Robinson, Rosemarie Hartman, Scott Lefler
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Publication number: 20030114661Abstract: The present invention provides novel disulfone compounds and methods of preparing and using those compounds to further prepare biologically relevant gem-disulfone analogs of natural enzyme substrates. Methods of using a variety of disulfone compounds as reagents capable of forming symmetrical and non-symmetrical &agr;, &bgr; unsaturated gem-disulfones are also provided. There is also provided a disulfone reagent which reacts with both aromatic and aliphatic aldehydes in good to moderate yield to give exclusively the trans isomer. In accordance with further aspects of the present invention, a methodology for stereospecifically preparing potential gem-disulfone enzyme inhibitors is provided. A synthetic design which allows easy substitution of functional groups so that a number of substrate analogs can be synthesized readily is also provided.Type: ApplicationFiled: November 5, 2002Publication date: June 19, 2003Applicant: The Arizona Disease Control Research CommissionInventors: Jacquelyn Gervay-Hague, Michael J. Hadd
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Patent number: 6576436Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. &agr;-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.Type: GrantFiled: December 9, 1999Date of Patent: June 10, 2003Assignee: The Arizona Disease Control Research CommissionInventors: Seth D. Rose, Steven R. Ottersberg, Karl J. Okolotowicz, Dale E. Robinson, Rosemarie Hartman, Scott Lefler
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Patent number: 6498277Abstract: The present invention provides novel disulfone compounds and methods of preparing and using those compounds to further prepare biologically relevant gem-disulfone analogs of natural enzyme substrates. Methods of using a variety of disulfone compounds as reagents capable of forming symmetrical and non-symmetrical &agr;, &bgr; unsaturated gem-disulfones are also provided. There is also provided a disulfone reagent which reacts with both aromatic and aliphatic aldehydes in good to moderate yield to give exclusively the trans isomer. In accordance with further aspects of the present invention, a methodology for stereospecifically preparing potential gem-disulfone enzyme inhibitors is provided. A synthetic design which allows easy substitution of functional groups so that a number of substrate analogs can be synthesized readily is also provided.Type: GrantFiled: June 14, 2000Date of Patent: December 24, 2002Assignee: The Arizona Disease Control Research CommissionInventors: Jacqueline Gervay-Hague, Michael J. Hadd
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Patent number: 6350777Abstract: Methoxy and ethoxy substituted 3-aroyl-2-arylbenzo[b]thiophenes and benzo[b]thiophene analogues are described for use in inhibiting tubulin polymerization. The compounds' use for treating tumor cells is also described. Additional aspects described here are certain diaryl ether benzo[b]thiophene derivatives. Also described are particular analogs derived from dihydronaphthalene which have proven particularly effective. Certain new benzofuran analogs are described, as well as certain sulfur oxide benzo[b]thiophene analogs. Important compounds described herein include the first nitrogen-containing derivatives of combretastatin. These include nitro, amino and azide combrdtastatin derivatives.Type: GrantFiled: December 15, 2000Date of Patent: February 26, 2002Assignees: Baylor University, Arizona Disease Control Research CommissionInventors: Kevin G. Pinney, George R. Pettit, Vani P. Mocharla, Maria del Pilar Mejia, Anupama Shirali