Photo of Dr. Gregory R Thatcher

Gregory R Thatcher


Hans W. Vahlteich Chair of Medicinal Chemistry, Pharmaceutical Sciences

Contact

Building & Room:

302 PHARM

Address:

833 South Wood Street, Chicago, IL, 60612

Office Phone:

(312) 355-5282

Office Phone:

(312) 413-0284

About

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.

Selected Publications

  • Xiong R, Patel H, Gutgesell LM, Zhao J, Delgado-Rivera LN, Pham TA, Zhao H, Carlson K, Martin TR, Katzenellenbogen J, Moore T, Tonetti D, Thatcher G. 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 TT, Michalsen BY, Xiong RC, Patel HR, Zhao H, Maximov P, Jordan V, Thatcher G, 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 JC, Piyankarage S, Wang SN, Wang YA, Pierce ET, Scism R, Michalsen BI, Xiong RL, Siklos MR, Bolton J, Thatcher G. 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 JE, Chandrasena RR, Qin ZL, Thatcher G, Bolton J. 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 BE, Chandrasena RR, Qin ZL, Sohn J, Thatcher G, Bolton J. 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 RC, Esala PA, Chen SM, Main MF, Lankin DR, Scism RL, Dietz B, Pauli G, Thatcher G, Bolton J. 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 ID, Edirisinghe PP, Hemachandra LR, Chandrasena ET, Choi JL, Wang YR, Bolton J, Thatcher G. 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 YW, Peng KB, van Breemen RR, Thatcher GL, Bolton J. 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 MT, Wang Y, Wang ZL, Qin ZR, Bolton J, Thatcher G. 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 JT, Wijewickrama GY, Edirisinghe PE, Gherezghiher TE, Hemachandra M, Lu PR, Chandrasena R, Molloy M, Tonetti D, Thatcher G. 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 HT, Qin Z, Wijewickrama GL, Lu MR, Wang Z, Bolton J, Thatcher G. 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 PE, Sohn JR, Qin ZL, Geacintov N, Thatcher G, Bolton J. 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 BT, Qin ZL, Wijewickrama GR, Edirisinghe P, Bolton J, Thatcher G. 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 LB, van Breemen RL, Bolton JR, Thatcher G. 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 ZT, Kastrati ID, Ashgodom RR, Lantvit DB, Overk CL, Choi YR, van Breemen R, Bolton J, Thatcher G. 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 MR, Overk CW, Kastrati IH, Peng KA, Yao PL, Qin ZR, Petukhov P, Bolton J, Thatcher G. 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 HR, Qin ZL, Thatcher G, Bolton J. 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 MW, Peng KR, Kastrati IH, Overk CL, Qin ZR, Yao P, Bolton J, Thatcher G. 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 ID, Lantvit DL, Qin ZR, Frasor J, Bolton J, Thatcher G. 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 BM, Dietz BL, Dunlap TD, Kastrati IR, Lantvit DL, Overk CR, Yao P, Qin Z, Bolton J, Thatcher G. 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 MC, Mehboob S, Mulhearn DR, Wang ZD, Yu HE, Thatcher GD, Santarsiero B, Johnson M, Mesecar A. 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 ZE, Kastrati IA, Chandrasena RL, Liu HR, Yao P, Petukhov P, Bolton J, Thatcher G. 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 HL, Bolton JR, Thatcher G. 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 JB, Li QL, Yang XR, van Breemen R, Bolton J, Thatcher G. 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 JB, Liu HR, van Breemen RL, Thatcher G, Bolton J. 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 HB, Liu JR, van Breemen RL, Thatcher G, Bolton J. 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 LB, Liu HR, Li WL, Zhang F, Luckie C, van Breemen R, Thatcher G, Bolton J. 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 LR, Thatcher G. Quinoids formed from estrogens and antiestrogens.. Methods in enzymology. 2004;378:110-23. doi:10.1016/S0076-6879(04)78006-4.
  • Toader VL, Xu XR, Nicolescu A, Yu L, Bolton J, Thatcher G. 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.