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Charles D Smith, PhD
Professor of Drug Discovery & Biomedical Sciences
College of Pharmacy
MUSC

Email: smithchd@musc.edu
 
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Charles D Smith, PhD

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Research Interest:

My research interests center on drug discovery and molecular pharmacology, particularly relating to sphingolipid signaling systems involved in cancer and inflammation. My research has produced more than 120 publications and multiple US and international patents, mostly focused on the identification of new targets for chemotherapy, and the design, synthesis and evaluation of new drug candidates. In the past several years, my laboratory focused on new targets in the sphingolipid metabolism pathway, including the sphingosine kinases and ceramidases that regulate tumor growth. In addition to my academic work, I am the Founder of Apogee Biotechnology Corporation, a drug discovery company that is developing proprietary compounds for the treatment of cancer and other diseases. Apogee is currently testing the first-in-class sphingosine kinase-2 inhibitor (ABC294640) in cancer patients at the Medical University of South Carolina.

Honors:
Endowed Chair in Cancer Drug Discovery, SmartState Center of Economic Excellence

Positions:
Director, Drug Discovery & Screening Shared Resource, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Dai L, Plaisance-Bonstaff K, Voelkel-Johnson C, Smith CD, Ogretmen B, Qin Z, Parsons C. Sphingosine kinase-2 maintains viral latency and survival for KSHV-infected endothelial cells. PLoS One. .9(7):e102314, 2014. PMCID: PMC4092155
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2.Qin Z, Dai L, Trillo-Tinoco J, Senkal C, Wang W, Reske T, Bonstaff K, Del Valle L, Rodriguez P, Flemington E, Voelkel-Johnson C, Smith CD, Ogretmen B, Parsons C. Targeting sphingosine kinase induces apoptosis and tumor regression for KSHV-associated primary effusion lymphoma. Mol Cancer Ther. .13(1):154-64, 2013. PMCID: PMC3918494
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3.Abdulghani J, Allen JE, Dicker DT, Liu YY, Goldenberg D, Smith CD, Humphreys R, El-Deiry WS. Sorafenib sensitizes solid tumors to Apo2L/TRAIL and Apo2L/TRAIL receptor agonist antibodies by the Jak2-Stat3-Mcl1 axis. PLoS One. .8(9):e75414, 2013. PMCID: PMC3784419
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4.Schwartz J, Holmuhamedov E, Zhang X, Lovelace GL, Smith CD, Lemasters JJ. Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter. Toxicol Appl Pharmacol. .273(1):172-9, 2013.
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5.Gangjee A, Kurup S, Smith CD. Synthesis of 5,7-disubstituted-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amines as microtubule inhibitors. Bioorg Med Chem. .21(5):1180-9, 2013. PMCID: PMC3582361
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6.Titchenell PM, Lin CM, Keil JM, Sundstrom JM, Smith CD, Antonetti DA. Novel atypical PKC inhibitors prevent vascular endothelial growth factor-induced blood-retinal barrier dysfunction. Biochem J. .446(3):455-67, 2012. PMCID: PMC3767384
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7.Gao P, Peterson YK, Smith RA, Smith CD. Characterization of isoenzyme-selective inhibitors of human sphingosine kinases. PLoS One. .7(9):e44543, 2012. PMCID: PMC3438171
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8.Baker DA, Eudaly J, Smith CD, Obeid LM, Gilkeson GS. Impact of sphingosine kinase 2 deficiency on the development of TNF-alpha-induced inflammatory arthritis. Rheumatol Int. .33(10):2677-81, 2012. PMCID: PMC3784643
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9.Liu Q, Rehman H, Shi Y, Krishnasamy Y, Lemasters JJ, Smith CD, Zhong Z. Inhibition of sphingosine kinase-2 suppresses inflammation and attenuates graft injury after liver transplantation in rats. PLoS One. .7(7):e41834, 2012. PMCID: PMC3405047
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10.Sun WY, Abeynaike LD, Escarbe S, Smith CD, Pitson SM, Hickey MJ, Bonder CS. Rapid histamine-induced neutrophil recruitment is sphingosine kinase-1 dependent. Am J Pathol. .180(4):1740-50, 2012.
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11.Yung LM, Wei Y, Qin T, Wang Y, Smith CD, Waeber C. Sphingosine kinase 2 mediates cerebral preconditioning and protects the mouse brain against ischemic injury. Stroke. .43(1):199-204, 2011. PMCID: PMC3246529
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12.Gao P, Smith CD. Ablation of sphingosine kinase-2 inhibits tumor cell proliferation and migration. Mol Cancer Res. .9(11):1509-19, 2011. PMCID: PMC3219805
View in: PubMed

13.Draper JM, Xia Z, Smith RA, Zhuang Y, Wang W, Smith CD. Discovery and evaluation of inhibitors of human ceramidase. Mol Cancer Ther. .10(11):2052-61, 2011. PMCID: PMC3213284
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14.Gallant JN, Allen JE, Smith CD, Dicker DT, Wang W, Dolloff NG, Navaraj A, El-Deiry WS. Quinacrine synergizes with 5-fluorouracil and other therapies in colorectal cancer. Cancer Biol Ther. .12(3):239-51, 2011.
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15.Wang W, Gallant JN, Katz SI, Dolloff NG, Smith CD, Abdulghani J, Allen JE, Dicker DT, Hong B, Navaraj A, El-Deiry WS. Quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and chemotherapeutic agents. Cancer Biol Ther. .12(3):229-38, 2011.
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16.Shi Y, Rehman H, Ramshesh VK, Schwartz J, Liu Q, Krishnasamy Y, Zhang X, Lemasters JJ, Smith CD, Zhong Z. Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion. J Hepatol. .56(1):137-45, 2011. PMCID: PMC3220779
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17.Smith CD. Your idea and your university: issues in academic technology transfer. J Investig Med. .59(5):752-7, 2011. PMCID: PMC3660085
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18.Gangjee A, Namjoshi OA, Keller SN, Smith CD. 2-Amino-4-methyl-5-phenylethyl substituted-7-N-benzyl-pyrrolo[2,3-d]pyrimidines as novel antitumor antimitotic agents that also reverse tumor resistance. Bioorg Med Chem. .19(14):4355-65, 2011. PMCID: PMC3138178
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19.Salas A, Ponnusamy S, Senkal CE, Meyers-Needham M, Selvam SP, Saddoughi SA, Apohan E, Sentelle RD, Smith C, Gault CR, Obeid LM, El-Shewy HM, Oaks J, Santhanam R, Marcucci G, Baran Y, Mahajan S, Fernandes D, Stuart R, Perrotti D, Ogretmen B. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood. .117(22):5941-52, 2011. PMCID: PMC3112039
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20.Antoon JW, White MD, Slaughter EM, Driver JL, Khalili HS, Elliott S, Smith CD, Burow ME, Beckman BS. Targeting NF?B mediated breast cancer chemoresistance through selective inhibition of sphingosine kinase-2. Cancer Biol Ther. .11(7):678-89, 2011. PMCID: PMC3084971
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21.Beljanski V, Lewis CS, Smith CD. Antitumor activity of sphingosine kinase 2 inhibitor ABC294640 and sorafenib in hepatocellular carcinoma xenografts. Cancer Biol Ther. .11(5):524-34, 2011. PMCID: PMC3087901
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22.Fitzpatrick LR, Green C, Maines LW, Smith CD. Experimental osteoarthritis in rats is attenuated by ABC294640, a selective inhibitor of sphingosine kinase-2. Pharmacology. .87(3-4):135-43, 2011.
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23.Beharry Z, Mahajan S, Zemskova M, Lin YW, Tholanikunnel BG, Xia Z, Smith CD, Kraft AS. The Pim protein kinases regulate energy metabolism and cell growth. Proc Natl Acad Sci U S A. .108(2):528-33, 2010. PMCID: PMC3021022
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24.Antoon JW, White MD, Meacham WD, Slaughter EM, Muir SE, Elliott S, Rhodes LV, Ashe HB, Wiese TE, Smith CD, Burow ME, Beckman BS. Antiestrogenic effects of the novel sphingosine kinase-2 inhibitor ABC294640. Endocrinology. .151(11):5124-35, 2010. PMCID: PMC2954724
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25.Chumanevich AA, Poudyal D, Cui X, Davis T, Wood PA, Smith CD, Hofseth LJ. Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase. Carcinogenesis. .31(10):1787-93, 2010. PMCID: PMC2981458
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26.Beljanski V, Knaak C, Zhuang Y, Smith CD. Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. Invest New Drugs. .29(6):1132-42, 2010. PMCID: PMC3089696
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27.Draper JM, Smith CD. DHHC20: a human palmitoyl acyltransferase that causes cellular transformation. Mol Membr Biol. .27(2-3):123-36, 2010. PMCID: PMC2893407
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28.Beljanski V, Knaak C, Smith CD. A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J Pharmacol Exp Ther. .333(2):454-64, 2010. PMCID: PMC2872961
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29.French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. .333(1):129-39, 2010. PMCID: PMC2846016
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30.Xia Z, Draper JM, Smith CD. Improved synthesis of a fluorogenic ceramidase substrate. Bioorg Med Chem. .18(3):1003-9, 2010. PMCID: PMC2841511
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31.Katz SI, Zhou L, Chao G, Smith CD, Ferrara T, Wang W, Dicker DT, El-Deiry WS. Sorafenib inhibits ERK1/2 and MCL-1(L) phosphorylation levels resulting in caspase-independent cell death in malignant pleural mesothelioma. Cancer Biol Ther. .8(24):2406-16, 2009. PMCID: PMC3052759
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32.Lin YW, Beharry ZM, Hill EG, Song JH, Wang W, Xia Z, Zhang Z, Aplan PD, Aster JC, Smith CD, Kraft AS. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. .115(4):824-33, 2009. PMCID: PMC2941996
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33.Beharry Z, Zemskova M, Mahajan S, Zhang F, Ma J, Xia Z, Lilly M, Smith CD, Kraft AS. Novel benzylidene-thiazolidine-2,4-diones inhibit Pim protein kinase activity and induce cell cycle arrest in leukemia and prostate cancer cells. Mol Cancer Ther. .8(6):1473-83, 2009. PMCID: PMC3415237
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34.Zhang F, Beharry ZM, Harris TE, Lilly MB, Smith CD, Mahajan S, Kraft AS. PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells. Cancer Biol Ther. .8(9):846-53, 2009.
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35.Draper JM, Smith CD. Palmitoyl acyltransferase assays and inhibitors (Review). Mol Membr Biol. .26(1):5-13, 2009. PMCID: PMC2635919
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36.Xia Z, Knaak C, Ma J, Beharry ZM, McInnes C, Wang W, Kraft AS, Smith CD. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. J Med Chem. .52(1):74-86, 2009.
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37.Tran MA, Smith CD, Kester M, Robertson GP. Combining nanoliposomal ceramide with sorafenib synergistically inhibits melanoma and breast cancer cell survival to decrease tumor development. Clin Cancer Res. .14(11):3571-81, 2008.
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38.Lesher AP, Kratz JM, Smith CD. Removal of embedded central venous catheters. J Pediatr Surg. .43(6):1030-4, 2008.
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39.Seaton KE, Smith CD. N-Myristoyltransferase isozymes exhibit differential specificity for human immunodeficiency virus type 1 Gag and Nef. J Gen Virol. .89(Pt 1):288-96, 2008. PMCID: PMC2888270
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40.Maines LW, Fitzpatrick LR, French KJ, Zhuang Y, Xia Z, Keller SN, Upson JJ, Smith CD. Suppression of ulcerative colitis in mice by orally available inhibitors of sphingosine kinase. Dig Dis Sci. .53(4):997-1012, 2007. PMCID: PMC2660406
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41.Plastaras JP, Kim SH, Liu YY, Dicker DT, Dorsey JF, McDonough J, Cerniglia G, Rajendran RR, Gupta A, Rustgi AK, Diehl JA, Smith CD, Flaherty KT, El-Deiry WS. Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation. Cancer Res. .67(19):9443-54, 2007.
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42.Hall MA, Cleveland JL. Clearing the TRAIL for Cancer Therapy. Cancer Cell. .12(1):4-6, 2007.
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43.Gangjee A, Yu J, Copper JE, Smith CD. Discovery of novel antitumor antimitotic agents that also reverse tumor resistance. J Med Chem. .50(14):3290-301, 2007. PMCID: PMC3858178
View in: PubMed

44.Draper JM, Xia Z, Smith CD. Cellular palmitoylation and trafficking of lipidated peptides. J Lipid Res. .48(8):1873-84, 2007. PMCID: PMC2895159
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45.Maines LW, French KJ, Wolpert EB, Antonetti DA, Smith CD. Pharmacologic manipulation of sphingosine kinase in retinal endothelial cells: implications for angiogenic ocular diseases. Invest Ophthalmol Vis Sci. .47(11):5022-31, 2006. PMCID: PMC2660407
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46.Ducker CE, Draper JM, Xia Z, Smith CD. In vitro and cellular assays for palmitoyl acyltransferases using fluorescent lipidated peptides. Methods. .40(2):166-70, 2006. PMCID: PMC2892119
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47.Sharma A, Tran MA, Liang S, Sharma AK, Amin S, Smith CD, Dong C, Robertson GP. Targeting mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in the mutant (V600E) B-Raf signaling cascade effectively inhibits melanoma lung metastases. Cancer Res. .66(16):8200-9, 2006. PMCID: PMC2777627
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48.Ducker CE, Griffel LK, Smith RA, Keller SN, Zhuang Y, Xia Z, Diller JD, Smith CD. Discovery and characterization of inhibitors of human palmitoyl acyltransferases. Mol Cancer Ther. .5(7):1647-59, 2006. PMCID: PMC2888271
View in: PubMed

49.French KJ, Upson JJ, Keller SN, Zhuang Y, Yun JK, Smith CD. Antitumor activity of sphingosine kinase inhibitors. J Pharmacol Exp Ther. .318(2):596-603, 2006. PMCID: PMC2660408
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50.Maines LW, Antonetti DA, Wolpert EB, Smith CD. Evaluation of the role of P-glycoprotein in the uptake of paroxetine, clozapine, phenytoin and carbamazapine by bovine retinal endothelial cells. Neuropharmacology. .49(5):610-7, 2005.
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51.Terracciano S, Bruno I, Bifulco G, Avallone E, Smith CD, Gomez-Paloma L, Riccio R. Synthesis, solution structure, and bioactivity of six new simplified analogues of the natural cyclodepsipeptide jaspamide. Bioorg Med Chem. .13(17):5225-39, 2005.
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52.Ducker CE, Upson JJ, French KJ, Smith CD. Two N-myristoyltransferase isozymes play unique roles in protein myristoylation, proliferation, and apoptosis. Mol Cancer Res. .3(8):463-76, 2005. PMCID: PMC2908404
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53.Sharma A, Trivedi NR, Zimmerman MA, Tuveson DA, Smith CD, Robertson GP. Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res. .65(6):2412-21, 2005.
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54.Ducker CE, Stettler EM, French KJ, Upson JJ, Smith CD. Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl acyltransferase. Oncogene. .23(57):9230-7, 2004. PMCID: PMC2908390
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55.Terracciano S, Bruno I, Bifulco G, Copper JE, Smith CD, Gomez-Paloma L, Riccio R. Synthesis, conformational analysis, and cytotoxicity of new analogues of the natural cyclodepsipeptide jaspamide. J Nat Prod. .67(8):1325-31, 2004.
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56.Lee BD, Li Z, French KJ, Zhuang Y, Xia Z, Smith CD. Synthesis and evaluation of dihydropyrroloquinolines that selectively antagonize P-glycoprotein. J Med Chem. .47(6):1413-22, 2004.
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57.French KJ, Zhuang Y, Schrecengost RS, Copper JE, Xia Z, Smith CD. Cyclohexyl-octahydro-pyrrolo[1,2-a]pyrazine-based inhibitors of human N-myristoyltransferase-1. J Pharmacol Exp Ther. .309(1):340-7, 2004.
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58.Hiol A, Caron JM, Smith CD, Jones TL. Characterization and partial purification of protein fatty acyltransferase activity from rat liver. Biochim Biophys Acta. .1635(1):10-9, 2003.
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59.French KJ, Schrecengost RS, Lee BD, Zhuang Y, Smith SN, Eberly JL, Yun JK, Smith CD. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. .63(18):5962-9, 2003.
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60.Varner AS, Ducker CE, Xia Z, Zhuang Y, De Vos ML, Smith CD. Characterization of human palmitoyl-acyl transferase activity using peptides that mimic distinct palmitoylation motifs. Biochem J. .373(Pt 1):91-9, 2003. PMCID: PMC1223475
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61.Lee BD, French KJ, Zhuang Y, Smith CD. Development of a syngeneic in vivo tumor model and its use in evaluating a novel P-glycoprotein modulator, PGP-4008. Oncol Res. .14(1):49-60, 2003.
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62.Varner AS, De Vos ML, Creaser SP, Peterson BR, Smith CD. A fluorescence-based high performance liquid chromatographic method for the characterization of palmitoyl acyl transferase activity. Anal Biochem. .308(1):160-7, 2002.
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63.Smith CD, Tecklenburg FW, Habib DM, Hughes MR, Hulsey TC, Ebeling M. Success factors and hurdles in quality improvement in a children's hospital. Semin Pediatr Surg. .11(1):12-9, 2002.
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64.De Vos ML, Lawrence DS, Smith CD. Cellular pharmacology of cerulenin analogs that inhibit protein palmitoylation. Biochem Pharmacol. .62(8):985-95, 2001.
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65.Xia Z, Smith CD. Efficient synthesis of a fluorescent farnesylated Ras peptide. J Org Chem. .66(15):5241-4, 2001.
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66.Xia Z, Smith CD. Total synthesis of dendroamide A, a novel cyclic peptide that reverses multiple drug resistance. J Org Chem. .66(10):3459-66, 2001.
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67.Lawrence DS, Copper JE, Smith CD. Structure-activity studies of substituted quinoxalinones as multiple-drug-resistance antagonists. J Med Chem. .44(4):594-601, 2001.
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68.Smith CD, Myers CB, Zilfou JT, Smith SN, Lawrence DS. Indoloquinoxaline compounds that selectively antagonize P-glycoprotein. Oncol Res. .12(5):219-29, 2000.
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69.Lawrence DS, Zilfou JT, Smith CD. Structure-activity studies of cerulenin analogues as protein palmitoylation inhibitors. J Med Chem. .42(24):4932-41, 1999.
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70.Morlière P, Mazière JC, Santus R, Smith CD, Prinsep MR, Stobbe CC, Fenning MC, Golberg JL, Chapman JD. Tolyporphin: a natural product from cyanobacteria with potent photosensitizing activity against tumor cells in vitro and in vivo. Cancer Res. .58(16):3571-8, 1998.
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71.Dinh TQ, Smith CD, Du X, Armstrong RW. Design, synthesis, and evaluation of the multidrug resistance-reversing activity of D-glucose mimetics of hapalosin. J Med Chem. .41(6):981-7, 1998.
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72.Zhang X, Minale L, Zampella A, Smith CD. Microfilament depletion and circumvention of multiple drug resistance by sphinxolides. Cancer Res. .57(17):3751-8, 1997.
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73.Smith CD, Zhang X. Mechanism of action cryptophycin. Interaction with the Vinca alkaloid domain of tubulin. J Biol Chem. .271(11):6192-8, 1996.
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74.Zhang X, Smith CD. Microtubule effects of welwistatin, a cyanobacterial indolinone that circumvents multiple drug resistance. Mol Pharmacol. .49(2):288-94, 1996.
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