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Photo of Gregory R Thatcher

Gregory R Thatcher

Hans W. Vahlteich Chair of Medicinal Chemistry, Medicinal Chemistry and Pharmacognosy

Contact Information

833 South Wood Street (781)
Chicago, IL 60612

Phone: (312) 355-5282

Fax: (312) 996-7107


Lab Phone: (312) 413-0284

Research Interests

Employing the tools of mechanistic organic chemistry and the ability to synthesize novel compounds, biomimetics are being developed as probes of biological systems. These mimetics have the capacity to further understanding of biological processes, chemical toxicology and in some cases to provide new drug candidates. This program is revealing new therapeutics for neurological disorders and for cancer.

Intellectual Contributions

Journal Article

  • Xiong R, Patel H, Gutgesell LM, Zhao J, Delgado-Rivera L, Pham TN, Zhao H, Carlson K, Martin T, Katzenellenbogen JA, Moore T, Tonetti D, Thatcher GR. "Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer.". Journal of medicinal chemistry. 2015;. doi:10.1021/acs.jmedchem.5b01276.
  • Molloy ME, White BE, Gherezghiher T, Michalsen BT, Xiong R, Patel H, Zhao H, Maximov PY, Jordan VC, Thatcher GR, Tonetti D. "Novel selective estrogen mimics for the treatment of tamoxifen-resistant breast cancer.". Molecular cancer therapeutics. 2014;13(11):2515-26. doi:10.1158/1535-7163.MCT-14-0319.
  • Hemachandra LP, Patel H, Chandrasena RE, Choi J, Piyankarage SC, Wang S, Wang Y, Pierce EN, Scism RA, Michalsen BT, Xiong R, Siklos MI, Bolton JL, Thatcher GR. "SERMs attenuate estrogen-induced malignant transformation of human mammary epithelial cells by upregulating detoxification of oxidative metabolites.". Cancer prevention research (Philadelphia, Pa.). 2014;7(5):505-15. doi:10.1158/1940-6207.CAPR-13-0296.
  • Michalsen BT, Gherezghiher TB, Choi J, Chandrasena RE, Qin Z, Thatcher GR, Bolton JL. "Selective estrogen receptor modulator (SERM) lasofoxifene forms reactive quinones similar to estradiol.". Chemical research in toxicology. 2012;25(7):1472-83. doi:10.1021/tx300142h.
  • Gherezghiher TB, Michalsen B, Chandrasena RE, Qin Z, Sohn J, Thatcher GR, Bolton JL. "The naphthol selective estrogen receptor modulator (SERM), LY2066948, is oxidized to an o-quinone analogous to the naphthol equine estrogen, equilenin.". Chemico-biological interactions. 2012;196(1-2):1-10. doi:10.1016/j.cbi.2012.01.004.
  • Hemachandra LP, Madhubhani P, Chandrasena R, Esala P, Chen S, Main M, Lankin DC, Scism RA, Dietz BM, Pauli GF, Thatcher GR, Bolton JL. "Hops (Humulus lupulus) inhibits oxidative estrogen metabolism and estrogen-induced malignant transformation in human mammary epithelial cells (MCF-10A).". Cancer prevention research (Philadelphia, Pa.). 2012;5(1):73-81. doi:10.1158/1940-6207.CAPR-11-0348.
  • Kastrati I, Edirisinghe PD, Hemachandra LP, Chandrasena ER, Choi J, Wang YT, Bolton JL, Thatcher GR. "Raloxifene and desmethylarzoxifene block estrogen-induced malignant transformation of human breast epithelial cells.". PloS one. 2011;6(11):e27876. doi:10.1371/journal.pone.0027876.
  • Wang Z, Chandrasena ER, Yuan Y, Peng KW, van Breemen RB, Thatcher GR, Bolton JL. "Redox cycling of catechol estrogens generating apurinic/apyrimidinic sites and 8-oxo-deoxyguanosine via reactive oxygen species differentiates equine and human estrogens.". Chemical research in toxicology. 2010;23(8):1365-73. doi:10.1021/tx1001282.
  • Peng KW, Chang M, Wang YT, Wang Z, Qin Z, Bolton JL, Thatcher GR. "Unexpected hormonal activity of a catechol equine estrogen metabolite reveals reversible glutathione conjugation.". Chemical research in toxicology. 2010;23(8):1374-83. doi:10.1021/tx100129h.
  • Kim HY, Sohn J, Wijewickrama GT, Edirisinghe P, Gherezghiher T, Hemachandra M, Lu PY, Chandrasena RE, Molloy ME, Tonetti D, Thatcher GR. "Click synthesis of estradiol-cyclodextrin conjugates as cell compartment selective estrogens.". Bioorganic & medicinal chemistry. 2010;18(2):809-21. doi:10.1016/j.bmc.2009.11.046.
  • Peng KW, Wang H, Qin Z, Wijewickrama GT, Lu M, Wang Z, Bolton JL, Thatcher GR. "Selective estrogen receptor modulator delivery of quinone warheads to DNA triggering apoptosis in breast cancer cells.". ACS chemical biology. 2009;4(12):1039-49. doi:10.1021/cb9001848.
  • Wang Z, Edirisinghe P, Sohn J, Qin Z, Geacintov NE, Thatcher GR, Bolton JL. "Development of a liquid chromatography electrospray ionization tandem mass spectrometry method for analysis of stable 4-hydroxyequilenin-DNA adducts in human breast cancer cells.". Chemical research in toxicology. 2009;22(6):1129-36. doi:10.1021/tx900063g.
  • Yu B, Qin Z, Wijewickrama GT, Edirisinghe P, Bolton JL, Thatcher GR. "Comparative methods for analysis of protein covalent modification by electrophilic quinoids formed from xenobiotics.". Bioconjugate chemistry. 2009;20(4):728-41. doi:10.1021/bc800435m.
  • Wang Z, Wijewickrama GT, Peng KW, Dietz BM, Yuan L, van Breemen RB, Bolton JL, Thatcher GR. "Estrogen Receptor {alpha} Enhances the Rate of Oxidative DNA Damage by Targeting an Equine Estrogen Catechol Metabolite to the Nucleus.". The Journal of biological chemistry. 2009;284(13):8633-42. doi:10.1074/jbc.M807860200.
  • Qin Z, Kastrati I, Ashgodom RT, Lantvit DD, Overk CR, Choi Y, van Breemen RB, Bolton JL, Thatcher GR. "Structural modulation of oxidative metabolism in design of improved benzothiophene selective estrogen receptor modulators.". Drug metabolism and disposition: the biological fate of chemicals. 2009;37(1):161-9. doi:10.1124/dmd.108.023408.
  • Chandrasena RE, Edirisinghe PD, Bolton JL, Thatcher GR. "Problematic detoxification of estrogen quinones by NAD(P)H-dependent quinone oxidoreductase and glutathione-S-transferase.". Chemical research in toxicology. 2008;21(7):1324-9. doi:10.1021/tx8000797.
  • Chang M, Overk CR, Kastrati I, Peng KW, Yao P, Qin ZH, Petukhov PA, Bolton JL, Thatcher GR. "Estrogenic activity of the equine estrogen metabolite, 4-methoxyequilenin.". Advances in experimental medicine and biology. 2008;617:601-7. doi:10.1007/978-0-387-69080-3_62.
  • Bolton JL, Thatcher GR. "Potential mechanisms of estrogen quinone carcinogenesis.". Chemical research in toxicology. 2008;21(1):93-101. doi:10.1021/tx700191p.
  • Liu H, Qin Z, Thatcher GR, Bolton JL. "Uterine peroxidase-catalyzed formation of diquinone methides from the selective estrogen receptor modulators raloxifene and desmethylated arzoxifene.". Chemical research in toxicology. 2007;20(11):1676-84. doi:10.1021/tx7001367.
  • Chang M, Peng KW, Kastrati I, Overk CR, Qin ZH, Yao P, Bolton JL, Thatcher GR. "Activation of estrogen receptor-mediated gene transcription by the equine estrogen metabolite, 4-methoxyequilenin, in human breast cancer cells.". Endocrinology. 2007;148(10):4793-802. doi:10.1210/en.2006-1568.
  • Overk CR, Peng KW, Asghodom RT, Kastrati I, Lantvit DD, Qin Z, Frasor J, Bolton JL, Thatcher GR. "Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene.". ChemMedChem. 2007;2(10):1520-6. doi:10.1002/cmdc.200700104.
  • Yu B, Dietz BM, Dunlap TL, Kastrati I, Lantvit DD, Overk CR, Yao P, Qin Z, Bolton JL, Thatcher GR. "Structural modulation of reactivity/activity in design of improved benzothiophene selective estrogen receptor modulators: induction of chemopreventive mechanisms.". Molecular cancer therapeutics. 2007;6(9):2418-28. doi:10.1158/1535-7163.MCT-07-0268.
  • May M, Mehboob S, Mulhearn DC, Wang Z, Yu H, Thatcher GR, Santarsiero BD, Johnson ME, Mesecar AD. "Structural and functional analysis of two glutamate racemase isozymes from Bacillus anthracis and implications for inhibitor design.". Journal of molecular biology. 2007;371(5):1219-37. doi:10.1016/j.jmb.2007.05.093.
  • Qin Z, Kastrati I, Chandrasena RE, Liu H, Yao P, Petukhov PA, Bolton JL, Thatcher GR. "Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity.". Journal of medicinal chemistry. 2007;50(11):2682-92. doi:10.1021/jm070079j.
  • Dowers TS, Qin ZH, Thatcher GR, Bolton JL. "Bioactivation of Selective Estrogen Receptor Modulators (SERMs).". Chemical research in toxicology. 2006;19(9):1125-37. doi:10.1021/tx060126v.
  • Liu H, Bolton JL, Thatcher GR. "Chemical modification modulates estrogenic activity, oxidative reactivity, and metabolic stability in 4'F-DMA, a new benzothiophene selective estrogen receptor modulator.". Chemical research in toxicology. 2006;19(6):779-87. doi:10.1021/tx050326r.
  • Liu J, Li Q, Yang X, van Breemen RB, Bolton JL, Thatcher GR. "Analysis of protein covalent modification by xenobiotics using a covert oxidatively activated tag: raloxifene proof-of-principle study.". Chemical research in toxicology. 2005;18(9):1485-96. doi:10.1021/tx0501738.
  • Liu J, Liu H, van Breemen RB, Thatcher GR, Bolton JL. "Bioactivation of the selective estrogen receptor modulator acolbifene to quinone methides.". Chemical research in toxicology. 2005;18(2):174-82. doi:10.1021/tx0497752.
  • Liu H, Liu J, van Breemen RB, Thatcher GR, Bolton JL. "Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids: 4'-fluoro substitution prevents quinoid formation.". Chemical research in toxicology. 2005;18(2):162-73. doi:10.1021/tx049776u.
  • Yu L, Liu H, Li W, Zhang F, Luckie C, van Breemen RB, Thatcher GR, Bolton JL. "Oxidation of raloxifene to quinoids: potential toxic pathways via a diquinone methide and o-quinones.". Chemical research in toxicology. 2004;17(7):879-88. doi:10.1021/tx0342722.
  • Bolton JL, Yu L, Thatcher GR. "Quinoids formed from estrogens and antiestrogens.". Methods in enzymology. 2004;378:110-23. doi:10.1016/S0076-6879(04)78006-4.
  • Toader V, Xu X, Nicolescu A, Yu L, Bolton JL, Thatcher GR. "Nitrosation, nitration, and autoxidation of the selective estrogen receptor modulator raloxifene by nitric oxide, peroxynitrite, and reactive nitrogen/oxygen species.". Chemical research in toxicology. 2003;16(10):1264-76. doi:10.1021/tx025641h.