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Philip M. Potter, PhD
Philip M. Potter, PhD

Philip M. Potter, PhD

Associate Member, St. Jude Faculty



PhD – University of Manchester, Manchester, England

Research Interests

  • Enzyme prodrug therapy
  • Esterase-mediated drug catalysis
  • Tumor-specific gene expressions

Activation of CPT-11

Selective inhibition of carboxylesterases

Structures of carboxylesterases

Selected Publications

Laizure SC, Hu ZY, Potter PM, Parker RB Inhibition of carboxylesterase-1 alters clopidogrel metabolism and disposition. Xenobiotica. 30:1-7, 2019.

Newman, S, Fan L, Pribnow A, Silkov A, Rice SV, Shao Y, Mulder H, Nakitandwe J, Shurtleff S, Azzato E, Wu G, Easton J, Nichols KE, Ellison D, Downing JR, Pappo A, Potter PM, Zhang J, Bahrami, A. Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas. Nature Med 25:597-602, 2019. 

Hatfield MJ, Binder RJ, Gannon R, Fratt EM, Bowling J, Potter PM. Potent, irreversible inhibition of human carboxylesterases by tanshinone anhydrides isolated from Salvia miltiorrhiza (“Danshen”). J Nat Prod, 81:2410-2418, 2018. 

Wierdl M, Tsurkan L, Chi L, Hatfield MJ, Tollemar V ,Bradley C, Chen X, Qu C, Potter PM. Targeting ALK in pediatric RMS does not induce antitumor activity in vivo. Cancer Chemother Pharmacol 82:251-263, 2018. 

Wu G, Fan L, Edmonson M, Shaw T, Boggs K, Easton J, Rusch M, Webb TR, Zhang J, Potter PM. Inhibition of SF3B1 by molecules targeting the spliceosome results in massive aberrant exon skipping. RNA 24:1056-1066, 2018. PMCID: 2984410

Binder RJ, Hatfield MJ, Chi L, Potter PM. Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors. Eur J Med Chem 149:79-89, 2018.

Shadrick WR, Slavish PJ, Chai, SC, Waddell B, Connelly M, Low JA, Tallant C, Young BM, Bharatham N, Knapp S, Boyd V, Morfouace M, Roussel M, Chen T, Lee RE; Guy, RK, Shelat A, Potter PM. Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors. Biorg Med Chem 26:25-36, 2018.

Hatfield MJ, Chen J, Fratt EM, Chi L, Bollinger JC, Binder RJ, Bowling J, Hyatt JL, Scarborough J, Jeffries C, Potter PM. Selective inhibitors of human liver carboxylesterase based upon a β-lapachone scaffold: Novel reagents for reaction profiling. J Med Chem 60:1568-1579, 2017.

Gutova M, Goldstein L, Metz M, Hovsepyan A, Tsurkan LG, Tirughana R, Tsaturyan L, Annala AJ, Synold TW, Wan Z, Seeger R, Anderson C, Moats RA, Potter PM, Aboody KS. Optimization of a neural stem cell-mediated carboxylesterase/irinotecan gene therapy for metastatic neuroblastoma. Mol Ther Oncolytics 14:67-76, 2016.

Wierdl M, Tsurkan L, Hatfield MJ, Potter PM. Tumor-selective targeting of drug metabolizing enzymes to treat metastatic cancer. Br J Pharmacol 173:2811-2818, 2016.

Hatfield MJ, Potter PM. Modulation of carboxylesterase-mediated drug metabolism by natural products. Am Pharmaceut Rev 19:40-4, 2016.

Argikar UA, Potter PM, Hutzler JM, Marathe PH. Challenges and opportunities with non-CYP enzymes: Aldehyde oxidase, carboxylesterase and UDP-glucuronosyl transferase: Focus on reaction phenotyping and prediction of human clearance. AAPS J 18:1391-1405, 2016.

Hatfield MJ, Umans RA, Hyatt JL, Edwards CC, Wierdl M, Tsurkan L, Taylor MR, Potter PM. Carboxylesterases: General detoxifying enzymes. Chem Biol Interact 259(Pt B): 327-331, 2016.

Shi Y, Joyner AS, Shadrick W, Palacios G, Lagisetti C, Potter PM, Sambucetti LC, Stamm S, Webb TR. Pharmacodynamic assays to facilitate pre-clinical and clinical development of pre-mRNA splicing modulatory drug candidates. Pharmacol Res Persp 3:e00158, 2015. 

Stewart E, Goshorn R, Bradley C, Griffiths LM, Benavente C, Twarog NR, Miller GM, Caufield W, Freeman BB 3rd, Bahrami A, Pappo A, Wu J, Loh A, Karlström Å, Calabrese C, Gordon B, Tsurkan L, Hatfield MJ, Potter PM, Snyder SE, Thiagarajan S, Shirinifard A, Sablauer A, Shelat AA, Dyer MA. Targeting the DNA repair pathway in Ewing sarcoma. Cell Rep 9:829-41, 2014.

Convertini P, Potter PM, Palacios G, de la Grange P, Webb TR, Stamm S. The splicing modulator Sudemycin E influences alternative splicing and changes chromatin modifications. Nucleic Acids Res 42:4947-61, 2014.

Webb TR, Joyner AS, Potter PM. The development and application of small molecule modulators of SF3b as therapeutic agents for cancer. Drug Discov Today 18:43-9, 2013.

Chen X, Stewart E, Shelat A, Qu C, Bahrami A, Hatley M, Wu G, Bradley C, McEvoy J, A, Pappo A, Spunt S, Valentine MB, Valentine V, Krafcik F, Lang WH, Wierdl M, Tsurkan L, Tollemar V, Federico SM, Morton C, Lu C, Ding L, Easton J, Rusch M, Nagahawatte P, Wang J, Parker M, Wei L, Hedlund E, Finkelstein D, Edmonson M, Shurtleff S, Boggs K, Mulder H, Yergeau D, Skapek S, Hawkins DS,  Ramirez N, Potter PM, Sandoval JA, Davidoff AM, Mardis ER, Wilson RK, Zhang J, Downing JR, Dyer MA. Targeting oxidative stress in embryonal rhabdomyosarcoma. Cancer Cell 24:710-24, 2013.

Kasai K, Nakashima H, Liu F, Kerr S, Wang J, Phelps M, Potter PM, Goins WB, Fernandez SA, and Chiocca EA. Toxicology and biodistribution studies for MGH2.1, and oncolytic virus that expresses two prodrug-activating genes, in combination with prodrugs. Mol Ther Nucleic Acids 2:e113, 2013.

Metz MZ, Gutova M, Lacey SF, Abramyants Y, Vo T, Gilchrist M, Ghoda LY, Barish ME, Brown CE, Najbauer J, Potter PM, Portnow J, Synold TW and Aboody KS.  Neural stem cell-mediated delivery of irinotecan-activating carboxylesterases to glioma: Implications for clinical use. Stem Cell Trans Med 2:983-92, 2013.

Cushman I, Cushman SM, Potter P, Casey PJ. Control of RhoA methylation by carboxylesterase I. J Biol Chem 288:19177-83, 2013.

Hatfield MJ, Tsurkan L, Hyatt JL, Edwards CC, Lemoff A, Yan B, Potter PM. Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza (“Danshen”). J Nat Prod 6:36-44, 2013.

Tsurkan L, Hatfield MJ, Hyatt JL, Carol C. Edwards CC, Potter PM. Inhibition of carboxylesterases by cholinesterase inhibitors. Chem-Biol Interact 203(1):226-30, 2013.

Crow JA, Victoria Bittles V, Borazjani A, Potter PM, Ross MK. Covalent inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by the carbamates JZL184 and URB597. Biochem Pharmacol 84:1215-22, 2012.

Kim J-K, Yuan H, Nie J, Leggas M, Potter PM, Rinehart J, Jay M, Lu X. High payload dual therapeutic-imaging nanocarriers for triggered tumor delivery. Small 8:2895-2903, 2012.

Ulrich DL, Lynch J, Wang Y, Fukuda Y, Nachagari D, Du G, Sun D, Fan Y, Tsurkan L, Potter PM, Rehg JE, and Schuetz J. The ATP-dependent mitochondrial porphyrin importer ABCB6 protects against phenylhydrazine toxicity. J Biol Chem 287:12679-90, 2012.

Crow JA, Bittles V, Herring KL, Borazjani A, Potter PM, Ross M. Inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by chlorpyrifos oxon, paraoxon and methyl paraoxon. Toxicol Appl Pharmacol 258:145-50, 2012.

Yu X, Sigler SC, Hossain D, Wierdl M, Gwaltney GR, Potter PM, Wadkins RM. Global and local molecular dynamics of a bacterial carboxylesterase provide insight into its catalytic mechanism. J Mol Model 18:2869-83, 2012.

Parkinson E, Hyatt JL, Hicks LD, Edwards CC, Yang B, Potter PM. Requirements for mammalian carboxylesterase inhibition by substituted ethane-1,2-diones. Bioorg Med Chem 19:4635-43, 2011.

Edwards JE, Khumbar A, Roberts A, Hemmert AC, Edwards CC, Potter PM, Redinbo MR. Immobilization of active human carboxylesterase 1 in biomimetic silica nanoparticles. Biotechnol Prog 27:863-9, 2011.

Fan L, Lagisetti C, Edwards CC, Webb TR, Potter PM. Sudemycins, novel small molecule analogues of FR904164, induce alternative gene splicing. ACS Chemical Biology 6:582-9, 2011.

Hemmert AC, Otto TC, Chica RA, Wierdl M, Lewis SL, Edwards CC, Tsurkan L, Cashman JR, Mayo SL, Potter PM, Cerasoli DM, Redinbo MR. Nerve agent hydrolysis activity designed into a human drug metabolism enzyme. PLoS One 18(6):e17441, 2011.

Hatfield MJ, Tsurkan L, Garrett M, Shaver T, Edwards CC, Hyatt JL, Hicks LD, Potter PM. Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11. Biochem Pharmacol 81:24-31, 2011.

Show More

Young BM, Hyatt JL, Bouck DC, Chen T, Hanumesh P, Price J, Boyd VA, Potter PM, Webb TR. Structure-activity relationships of substituted 1-Pyridyl-2-phenyl-1,2-ethanediones: potent, selective carboxylesterase inhibitors. J Med Chem 53:8709-8715, 2010.

Hatfield MJ, Tsurkan L, Hyatt JL, Yu X, Edwards CC, Hicks LD, Wadkins RM, Potter PM. Biochemical and molecular analysis of carboxylesterase-mediated hydrolysis of cocaine and heroin. Br J Pharmacol 160:1916-1928, 2010.

Hicks LD, Hyatt JL, Stoddard S, Tsurkan L, Edwards CC, Wadkins RM, Potter PM. Improved, selective human intestinal carboxylesterase inhibitors designed to modulate 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (irinotecan; CPT-11) toxicity. J Med Chem 52:3742-3752, 2009.

Wierdl M, Tsurkan L, Hyatt JL, Hatfield MJ, Edwards CC, Danks MK, Redinbo MR, Potter PM. An improved human carboxylesterase for use in enzyme/prodrug therapy with CPT-11. Cancer Gene Ther 15:183-192, 2008.

Hyatt JL, Wadkins RM, Tsurkan L, Hicks L, Hatfield MJ, Edwards CC, Ross CR, Cantalupo SA, Crundwell G, Guy RK, Potter PM. Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. J Med Chem 50:5727-5734, 2007.

Danks MK Yoon KJ, Bush RA, Remack JS, Wierdl M, Tsurkan L, Kim SU, Garcia E, Metz M, Najbauer J, Potter PM, Aboody KS, Tumor-targeted enzyme/prodrug therapy mediates long-term disease-free survival of mice bearing disseminated neuroblastoma. Cancer Res 67:22-25, 2007.

Aboody KS, Bush RA, Garcia E, Metz M, Najbauer J, Justus KA, Phelps DA, Remack JS, Yoon KJ, Gillespie S, Kim SU, Glackin C, Potter PM, Danks MK. Development of a tumor-selective approach to treat metastatic cancer. PLoS One 1:e23; 1-10, 2006. Editorials PLoS Medicine 3:e482, 2182-2183, 2006; Nature Clin Practice Oncology 4:279-80, 2007; PLoS Medicine 3: e482, 2006.

Hyatt JL, Tsurkan L, Wierdl M, Edwards CC, Danks MK, Potter PM. Intracellular inhibition of carboxylesterases by benzil: Modulation of CPT-11 cytotoxicity. Mol Cancer Therap 5:2281-2288, 2006.

Harel M, Hyatt JL, Brumshtein B, Morton CL, Wadkins RM, Silman I, Sussman JL, Potter PM. The 3D structure of the anticancer prodrug CPT-11 with Torpedo californica acetylcholinesterase rationalizes its inhibitory action on AChE and its hydrolysis by butyrylcholinesterase and carboxylesterase. Chem Biol Int 157-158:153-157, 2005.

Wadkins RM, Hyatt JL, Wei X, Yoon KJP, Wierdl M, Edwards CC, Morton CL, Obenauer JC, Damodaran K, Beroza P, Danks MK, Potter PM. Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases. J Med Chem 48:2906-2915, 2005.

Wadkins RM, Hyatt JL, Yoon KJ, Morton CL, Lee RE, Damodaran K, Beroza P, Danks MK, Potter PM. Identification of novel selective human intestinal carboxylesterase inhibitors for the amelioration of CPT-11 induced diarrhea: Synthesis, QSAR analysis, mechanism of action and biological activity. Mol Pharmacol 65:1336-1343, 2004.

Stubdhal H, Perin N, Lemmon M, Holman P, Bauzon M, Potter PM, Danks MK, Fattaey A, Dubensky T, Johnson L. A prodrug strategy using ONYX-015-based replicating adenoviruses to deliver rabbit liver carboxylesterase to tumor cells for conversion of CPT-11 to SN-38. Cancer Res 63:6900-6908, 2003.

Wierdl M, Wall A, Morton CL, Danks MK, Schuetz JD, Potter PM. Carboxylesterase-mediated sensitization of human tumor cells to CPT-11 cannot override BCRP-mediated drug resistance. Mol Pharm 64:279-288, 2003.

Bencharit S, Morton CL, Hyatt, JL, Kuhn P, Danks MK, Potter PM, Redinbo MR. Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: From binding promiscuity to selective inhibition. Chem and Biol 10:341-349, 2003. *Preview, Chem and Biol 10:295-297, 2003. Review,  Nat Rev Drug Discov 2:511, 2003.

Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR. Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol 10:349-356, 2003. *Review, Nat Rev Drug Discov 2:511, 2003.

Bencharit S, Morton CL, Howard-Williams EL, Danks, MK, Potter PM, Redinbo MR. Structural insights into CPT-11 activation by mammalian carboxylesterases. Nature Struct Biol 9:337-342, 2002

Meck M, Wierdl M, Wagner L, Burger R, Harris LC, Potter PM, Danks MK. A VDEPT approach to purging neuroblastoma cells from hematopoeitic cells using adenovirus encoding rabbit carboxylesterase and CPT-11. Cancer Res 61:5083-5089, 2001.

Wierdl M, Morton CL, Weeks JK, Danks MK, Harris LC, Potter PM. Sensitization of human tumor cells to CPT-11 via adenoviral-mediated delivery of a rabbit liver carboxylesterase. Cancer Res 61:5078-5082, 2001.

Khanna R, Morton CL, Wierdl M, Danks MK, Potter PM. Proficient metabolism of CPT-11 by a human intestinal carboxylesterase. Cancer Res 60:4725-4728, 2000.

Danks MK, Morton CL, Krull EJ, Cheshire PJ, Richmond LB, Naeve CW, Pawlik CA, Houghton PJ, Potter PM. Comparison of activation of CPT-11 by rabbit and human carboxylesterase for use in enzyme/prodrug therapy. Clin Cancer Res 5:917-924, 1999.

Morton CL, Wadkins R, Danks MK, Potter PM: The anticancer drug CPT-11 is a potent inhibitor of acetylcholinesterases but is activated to SN-38 by butyrylcholinesterases. Cancer Res 59:1458-1463, 1999.

Potter PM, Wolverton JS, Morton CL, Wierdl M, Danks MK. Cellular localization domains of a rabbit and a human carboxylesterase: influence on CPT-11 metabolism by the rabbit enzyme. Cancer Res 58:3627-3632, 1998.

Potter PM, Pawlik CA, Morton CL, Naeve CW, Danks MK. Isolation and partial characterization of a cDNA encoding a rabbit liver carboxylesterase that activates the prodrug CPT-11. Cancer Res 58:2646-2651, 1998.

Last update: September 2019