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RP-101

RP101, also known as BvdU, is a nucleoside analog which has shown, in several preclinical and clinical studies, the potential to prevent the induction of resistance to chemotherapy by suppressing genes involved in development of that resistance and enhancing sensitivity to chemotherapy.

Discontinuation of RP-101: FOSTER CITY, CA, Oct 02, 2009 (MARKETWIRE via COMTEX) -- SciClone Pharmaceuticals, Inc. (NASDAQ: SCLN) today announced the discontinuation of the investigational treatments under its randomized, placebo-controlled, double-blind Phase 2 trial that is evaluating RP101 -- a nucleoside analog known as BvdU -- for the treatment of late-stage pancreatic cancer. This decision followed the recommendation of the Data Safety Monitoring Committee (DSMC) with oversight responsibility for this clinical trial that was based upon the data reviewed at the most recent DSMC meeting. Further details will be reported when these data have been unblinded and reviewed by SciClone. "We are disappointed with the discontinuation of this study and we will continue to evaluate future opportunities to bring new and effective treatments to these patients," said Friedhelm Blobel, PhD., President and Chief Executive Officer of SciClone. (source: http://investor.sciclone.com/releasedetail.cfm?ReleaseID=419435).

Current developer:    SciClone Pharmaceuticals.

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57: Degrève B, De Clercq E, Balzarini J. Selection of HSV-1 TK gene-transfected murine mammary carcinoma cells resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and ganciclovir (GCV). Gene Ther. 2000 Sep;7(18):1543-52. PubMed PMID: 11021592.

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64: Balzarini J, Degrève B, Hatse S, De Clercq E, Breuer M, Johansson M, Huybrechts R, Karlsson A. The multifunctional deoxynucleoside kinase of insect cells is a target for the development of new insecticides. Mol Pharmacol. 2000 Apr;57(4):811-9. PubMed PMID: 10727530.

65: Zhang Y, Schols D, De Clercq E. Selective activity of various antiviral compounds against HHV-7 infection. Antiviral Res. 1999 Aug;43(1):23-35. PubMed PMID: 10480261.

66: Degrève B, De Clercq E, Balzarini J. Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues. Gene Ther. 1999 Feb;6(2):162-70. PubMed PMID: 10435100.

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70: Afouna MI, Mehta SC, Ghanem AH, Higuchi WI, Kern ER, De Clercq E, El-Shattawy HH. Assessment of correlation between skin target site free drug concentration and the in vivo topical antiviral efficacy in hairless mice for (E)-5-(2-bromovinyl)-2'-deoxyuridine and acyclovir formulations. J Pharm Sci. 1998 Aug;87(8):917-21. PubMed PMID: 9687333.

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80: Reymen D, Naesens L, Balzarini J, Holý A, Dvoráková H, De Clercq E. Antiviral activity of selected acyclic nucleoside analogues against human herpesvirus 6. Antiviral Res. 1995 Dec;28(4):343-57. PubMed PMID: 8669893.

81: Kim JH, Kim SH, Kolozsvary A, Brown SL, Kim OB, Freytag SO. Selective enhancement of radiation response of herpes simplex virus thymidine kinase transduced 9L gliosarcoma cells in vitro and in vivo by antiviral agents. Int J Radiat Oncol Biol Phys. 1995 Nov 1;33(4):861-8. PubMed PMID: 7591895.

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85: Mazzacano CA, Fallon AM. Evaluation of a viral thymidine kinase gene for suicide selection in transfected mosquito cells. Insect Mol Biol. 1995 May;4(2):125-34. PubMed PMID: 7551194.

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89: Berry M, Easty DL, Declercq E. Effect of antivirals on human corneal cells in vitro. Toxicol In Vitro. 1994 Aug;8(4):727-9. PubMed PMID: 20692997.

90: Snoeck R, Andrei G, De Clercq E. Chemotherapy of varicella zoster virus infections. Int J Antimicrob Agents. 1994 Aug;4(3):211-26. PubMed PMID: 18611613.

91: Olivier A, Creuven I, Evrard C, Evrard G, Dory M, van Aerschot A, Wigerinck P, Herdewijn P, Durant F. Stereoelectronic properties of five anti-HSV-1 2'-deoxynucleosides analogues with heterocyclic substituents in the 5-position: a comparison with BVDU. Antiviral Res. 1994 Aug;24(4):289-304. PubMed PMID: 7993074.

92: Wilber BA, Docherty JJ. Analysis of the thymidine kinase of a herpes simplex virus type 1 isolate that exhibits resistance to (E)-5-(2-bromovinyl)-2'-deoxyuridine. J Gen Virol. 1994 Jul;75 ( Pt 7):1743-7. PubMed PMID: 8021603.

93: Snoeck R, Gérard M, Sadzot-Delvaux C, Andrei G, Balzarini J, Reymen D, Ahadi N, De Bruyn JM, Piette J, Rentier B, et al. Meningoradiculoneuritis due to acyclovir-resistant varicella zoster virus in an acquired immune deficiency syndrome patient. J Med Virol. 1994 Apr;42(4):338-47. PubMed PMID: 8046424.

94: Balzarini J, Bohman C, De Clercq E. Differential mechanism of cytostatic effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, 9-(1,3-dihydroxy-2-propoxymethyl)guanine, and other antiherpetic drugs on tumor cells transfected by the thymidine kinase gene of herpes simplex virus type 1 or type 2. J Biol Chem. 1993 Mar 25;268(9):6332-7. PubMed PMID: 8384209.

95: De Clercq E. Antiviral agents: characteristic activity spectrum depending on the molecular target with which they interact. Adv Virus Res. 1993;42:1-55. Review. PubMed PMID: 8430518.

96: Fardeau C, Langlois M, Nugier F, Asselot C, Aymard M, Denis J. Cross-resistances to antiviral drugs of IUdR-resistant HSV1 in rabbit keratitis and in vitro. Cornea. 1993 Jan;12(1):19-24. PubMed PMID: 8384543.

97: Snoeck R, Schols D, Sadzot-Delvaux C, Cloes JM, Andrei G, De Clercq E, Piette J, Rentier B. Flow cytometric method for the detection of gpI antigens of varicella zoster virus and evaluation of anti-VZV agents. J Virol Methods. 1992 Aug;38(2):243-54. PubMed PMID: 1325472.

98: Oshiro Y, Piper CE, Soelter SG, Balwierz PS, Garriott ML. Genotoxic properties of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU). Fundam Appl Toxicol. 1992 May;18(4):491-8. PubMed PMID: 1526360.

99: Suzutani T, Machida H. Analysis of toxic and mutagenic activities of antiherpesvirus nucleosides against HeLa cells and herpes simplex virus type 1. Mutat Res. 1992 May;267(1):125-31. PubMed PMID: 1373847.

100: Andrei G, Snoeck R, Goubau P, Desmyter J, De Clercq E. Comparative activity of various compounds against clinical strains of herpes simplex virus. Eur J Clin Microbiol Infect Dis. 1992 Feb;11(2):143-51. PubMed PMID: 1327785.

101: Tandon M, Singh S, Xu L, Kumar P, Wiebe LI, Knaus EE, Gati WP, Tempest ML. Synthesis and biological activity of 5-(2,2-difluorocyclopropyl)-2'-deoxyuridine deoxyuridine diastereomers. Drug Des Discov. 1992;9(1):79-91. PubMed PMID: 1333829.

102: Power WJ, Benedict-Smith A, Hillery M, Brady K, Collum LM. Randomised double-blind trial of bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration. Br J Ophthalmol. 1991 Nov;75(11):649-51. PubMed PMID: 1751456; PubMed Central PMCID: PMC1042518.

103: Maudgal PC, De Clercq E. Effects of phosphonylmethoxyalkyl-purine and -pyrimidine derivatives on TK+ and TK- HSV-1 keratitis in rabbits. Antiviral Res. 1991 Jul;16(1):93-100. PubMed PMID: 1663731.

104: Tandon M, Singh S, Wiebe LI, Knaus EE, Gati WP, Tempest ML. Synthesis of the diastereomers of 5-(2,2-dichlorocyclopropyl)- and 5-(2-chlorocyclopropyl)-2'-deoxyuridine, and the antiviral and cytotoxic activity of these and bromo analogues. Drug Des Deliv. 1991 Jul;7(4):295-307. PubMed PMID: 1657019.

105: Maudgal PC, De Clercq E. (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine in the therapy of thymidine kinase-positive and -deficient herpes simplex virus experimental keratitis. Invest Ophthalmol Vis Sci. 1991 May;32(6):1816-20. PubMed PMID: 1851733.

106: Power WJ, Benedict-Smith A, Hillery M, Brady K, Collum LM. Bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration: a double blind controlled study. Curr Eye Res. 1991;10 Suppl:183-7. PubMed PMID: 1907535.

107: Docherty JJ, Dobson AT, Trimble JJ, Jennings BA. Herpes simplex virus type 1 that exhibits herpes simplex virus type 2 sensitivity to (E)-5-(2-bromovinyl)-2'-deoxyuridine. Intervirology. 1991;32(5):308-15. PubMed PMID: 1657822.

108: Shiraki K, Vonka V, De Clercq E, Rapp F. Selection of L cell sublines resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine. Intervirology. 1991;32(4):228-33. PubMed PMID: 1650764.

109: Taylor JL, Punda-Polic V, O'Brien WJ. Combined anti-herpes virus activity of nucleoside analogs and interferon. Curr Eye Res. 1991;10 Suppl:205-11. PubMed PMID: 1650669.

110: Maudgal PC, De Clercq E. Bromovinyldeoxyuridine treatment of herpetic keratitis clinically resistant to other antiviral agents. Curr Eye Res. 1991;10 Suppl:193-9. PubMed PMID: 1650667.

111: Maudgal PC, De Clercq E. Efficacy of 9-(2-phosphonylmethoxyethyl)adenine in the therapy of TK+ and TK- herpes simplex virus experimental keratitis. Curr Eye Res. 1991;10 Suppl:139-42. PubMed PMID: 1650660.

112: Veerisetty V, Balasubramaniam NK, Gentry GA. Equine herpes virus 1 and pseudorabies virus resistance to 2'-fluoropyrimidine analogs and to bromovinyldeoxyuridine: implications for dTMP kinase activity. Acta Virol. 1990 Dec;34(6):568-73. PubMed PMID: 1983184.

113: Langford MP, Colacino JM, Kaiwar R, Mahjoub SB, Ganley JP. Cytopathogenicity, drug susceptibility, and thymidine kinase activity of a retinovirulent herpes simplex virus type 2. J Med Virol. 1990 Aug;31(4):301-5. PubMed PMID: 2176674.

114: Farrow SN, Jones AS, Kumar A, Walker RT, Balzarini J, De Clercq E. Synthesis and biological properties of novel phosphotriesters: a new approach to the introduction of biologically active nucleotides into cells. J Med Chem. 1990 May;33(5):1400-6. PubMed PMID: 2329561.

115: Iigo M, Miwa M, De Clercq E. Optimal treatment regimens for 5'-deoxy-5-fluorouridine, with or without (E)-5-(2-bromovinyl)-2'-deoxyuridine, against various tumors in mice. Jpn J Cancer Res. 1990 Apr;81(4):431-5. PubMed PMID: 2142152.

116: De Clercq E. Selective virus inhibitors. Microbiologica. 1990 Apr;13(2):165-78. Review. PubMed PMID: 1693749.

117: Balzarini J, De Clercq E, Baumgartner H, Bodenteich M, Griengl H. Carbocyclic 5-iodo-2'-deoxyuridine (C-IDU) and carbocyclic (E)-5-(2-bromovinyl)-2'-deoxyuridine (C-BVDU) as unique examples of chiral molecules where the two enantiomeric forms are biologically active: interaction of the (+)- and (-)-enantiomers of C-IDU and C-BVDU with the thymidine kinase of herpes simplex virus type 1. Mol Pharmacol. 1990 Mar;37(3):395-401. PubMed PMID: 2156153.

118: Iigo M, Nishikata K, Nakajima Y, Hoshi A, De Clercq E. Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on life-span and 5-fluorouracil metabolism in mice with hepatic metastases. Eur J Cancer. 1990;26(10):1089-92. PubMed PMID: 2148885.

119: Jackson LS, Stafford JE. Evaluation of antisera to 5-(2-bromo-E-ethenyl)-2'-deoxyuridine for the radioimmunoassay of a potent antiviral agent. J Pharmacol Methods. 1989 Sep;22(2):125-32. PubMed PMID: 2811389.

120: van Bijsterveld OP, Meurs PJ, de Clercq E, Maudgal PC. Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study. Br J Ophthalmol. 1989 Aug;73(8):604-7. PubMed PMID: 2669938; PubMed Central PMCID: PMC1041826.

121: Palú G, Bevilacqua F, Biasolo MA, Parolin C, Tognon M, Romanelli MG, Meloni GA. Acyclovir resistance in herpes simplex virus type 1: biochemical and functional studies on the thymidine kinase of the highly resistant R100 strain. Virus Res. 1989 Aug;13(4):303-18. PubMed PMID: 2554611.

122: Balzarini J, Baumgartner H, Bodenteich M, De Clercq E, Griengl H. Synthesis and antiviral activity of the enantiomeric forms of carba-5-iodo-2'-deoxyuridine and carba-(E)-5-(2-bromovinyl)-2'-deoxyuridine. J Med Chem. 1989 Aug;32(8):1861-5. PubMed PMID: 2547072.

123: Iigo M, Nishikata K, Nakajima Y, Hoshi A, Okudaira N, Odagiri H, De Clercq E. Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5'-deoxy-5-fluorouridine against adenocarcinoma 755 in mice. Correlation with pharmacokinetics of plasma 5-fluorouracil levels. Biochem Pharmacol. 1989 Jun 15;38(12):1885-9. PubMed PMID: 2525905.

124: Benad A, Richter E. [BVDU therapy in herpes corneae]. Klin Monbl Augenheilkd. 1989 Jun;194(6):424-6. German. PubMed PMID: 2761189.

125: Balzarini J, De Clercq E. Inhibitory effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and related compounds on herpes simplex virus (HSV)-infected cells and HSV thymidine kinase gene-transformed cells. Methods Find Exp Clin Pharmacol. 1989 Jun;11(6):379-89. Review. PubMed PMID: 2545982.

126: Coen DM, Irmiere AF, Jacobson JG, Kerns KM. Low levels of herpes simplex virus thymidine- thymidylate kinase are not limiting for sensitivity to certain antiviral drugs or for latency in a mouse model. Virology. 1989 Feb;168(2):221-31. PubMed PMID: 2536980.

127: Ameye C, Sundmacher R, de Clercq E. Topical BVDU plus low-dosage steroids in the treatment of chronic relapsing zoster keratouveitis. A pilot study. Graefes Arch Clin Exp Ophthalmol. 1989;227(2):118-22. PubMed PMID: 2656415.

128: Lazarus HM, Imperia PS, Botti RE, Mack RJ, Lass JH. An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents. Lens Eye Toxic Res. 1989;6(1-2):59-85. PubMed PMID: 2488034.

129: Scheck AC, Wigdahl B, Rapp F. Transcriptional activity of the herpes simplex virus genome during establishment, maintenance, and reactivation of in vitro virus latency. Intervirology. 1989;30(3):121-36. PubMed PMID: 2473963.

130: Marquardt H, Westendorf J, Schaefer A, Boldt J, De Clercq E, Marquardt H. Mutagenic and antimutagenic effects of 5-substituted 2'-deoxyuridines depending on the nature of the 5-substituent. Arzneimittelforschung. 1988 Dec;38(12):1820-4. PubMed PMID: 3072958.

131: Wutzler P, Wutke K, Bärwolff D, Reefschläger J. [5-(2-bromovinyl)-2'-deoxyuridine therapy of herpes zoster diseases in patients with malignant primary diseases]. Z Gesamte Inn Med. 1988 Dec 1;43(23):677-80. German. PubMed PMID: 2854331.

132: Olofsson S, Milla M, Hirschberg C, De Clercq E, Datema R. Inhibition of terminal N- and O-glycosylation specific for herpesvirus-infected cells: mechanism of an inhibitor of sugar nucleotide transport across Golgi membranes. Virology. 1988 Oct;166(2):440-50. PubMed PMID: 2845656.

133: Griengl H, Hayden W, Penn G, De Clercq E, Rosenwirth B. Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity. J Med Chem. 1988 Sep;31(9):1831-9. PubMed PMID: 2842506.

134: Chengelis CP, Port CD, Dickie BC. The chronic toxicity of bromovinyldeoxyuridine in beagle dogs. Fundam Appl Toxicol. 1988 Jul;11(1):143-54. PubMed PMID: 3209011.

135: Imperia PS, Lazarus HM, Dunkel EC, Pavan-Langston D, Geary PA, Lass JH. An in vitro study of ophthalmic antiviral agent toxicity on rabbit corneal epithelium. Antiviral Res. 1988 Jul;9(4):263-72. PubMed PMID: 3144240.

136: Lin JC, Machida H. Comparison of two bromovinyl nucleoside analogs, 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil and E-5-(2-bromovinyl)-2'-deoxyuridine, with acyclovir in inhibition of Epstein-Barr virus replication. Antimicrob Agents Chemother. 1988 Jul;32(7):1068-72. PubMed PMID: 2847639; PubMed Central PMCID: PMC172345.

137: Iigo M, Araki E, Nakajima Y, Hoshi A, De Clercq E. Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5-fluorouracil against adenocarcinoma 755 in mice. Increased therapeutic index and correlation with increased plasma 5-fluorouracil levels. Biochem Pharmacol. 1988 Apr 15;37(8):1609-13. PubMed PMID: 3358790.

138: Keizer HJ, Pauwels R, Landuyt W, Balzarini J, van der Schueren E, De Clercq E. Combined effects of bromovinyldeoxyuridine and fractionated or continuous administration of 5-fluorouracil in P388 leukemia-bearing mice. Cancer Lett. 1988 Mar;39(2):217-23. PubMed PMID: 3359416.

139: Kimura T, Nishizawa T, Yoshimizu M, De Clercq E. Inhibitory activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine on the salmonid herpesviruses, Oncorhynchus masou virus (OMV) and Herpesvirus salmonis. Microbiol Immunol. 1988;32(1):57-65. PubMed PMID: 3374404.

140: Jones AS, Sayers JR, Walker RT, De Clercq E. Synthesis and antiviral properties of (E)-5-(2-bromovinyl)-2'-deoxycytidine-related compounds. J Med Chem. 1988 Jan;31(1):268-71. PubMed PMID: 2826786.

141: Trousdale MD, Robin JB, Willey DE, De Clercq E. Intentional reactivation of latent ocular herpes infection during BVDU therapy. Curr Eye Res. 1987 Dec;6(12):1471-7. PubMed PMID: 2827960.

142: De Fazio G, Vicente M, De Clercq E. Antiviral effects of dihydroxypropyladenine [RS)-DHPA) and bromovinyldeoxyuridine (BVDU) on plant viruses. Antiviral Res. 1987 Nov;8(4):163-9. PubMed PMID: 3446016.

143: Helbig B, Sauerbrei A, Klöcking R, Wutzler P, Wicht N, Wiedemann U, Herrmann G. Therapeutic effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, caffeic acid oxidation product, and trisodiumphosphonoformate on cutaneous herpes simplex virus type 1 infection in guinea pigs. J Med Virol. 1987 Nov;23(3):303-9. PubMed PMID: 2828526.

144: Bubley GJ, Balzarini J, Crumpacker CS, de Clercq E, Schnipper LE. The effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on DNA repair and mutagenesis of herpes simplex virus type 1. Virology. 1987 Nov;161(1):242-4. PubMed PMID: 2823464.

145: Temicheva EV, Malinovskaia VV, Manakhova LS, Mironova LL, Galegov GA. [Combined action of nucleosides and alpha-interferon in inhibiting the reproduction of the herpes simplex type-II virus]. Biull Eksp Biol Med. 1987 Oct;104(10):490-2. Russian. PubMed PMID: 2823929.

146: Sági J, De Clercq E, Szemzö A, Csárnyi A, Kovács T, Otvös L. Incorporation of the carbocyclic analogue of (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate into a synthetic DNA. Biochem Biophys Res Commun. 1987 Sep 30;147(3):1105-12. PubMed PMID: 3663210.

147: Balzarini J, De Clercq E, Verbruggen A, Ayusawa D, Shimizu K, Seno T. Thymidylate synthase is the principal target enzyme for the cytostatic activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine against murine mammary carcinoma (FM3A) cells transformed with the herpes simplex virus type 1 or type 2 thymidine kinase gene. Mol Pharmacol. 1987 Sep;32(3):410-6. PubMed PMID: 2823092.

148: Kit S, Ichimura H, De Clercq E. Differential metabolism of (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) by equine herpesvirus type 1- and herpes simplex virus-infected cells. Antiviral Res. 1987 Aug;8(1):41-51. PubMed PMID: 2825591.

149: Párkányi L, Kálmán A, Czugler M, Kovács T, Walker RT. A comparison of the conformations adopted by some 5-bromovinyl-2'-deoxyuridines and a correlation with their antiviral properties: an X-ray study. Nucleic Acids Res. 1987 May 26;15(10):4111-21. PubMed PMID: 3588286; PubMed Central PMCID: PMC340835.

150: Baba M, Shigeta S, De Clercq E. Serum and urine concentrations of oral bromovinyldeoxyuridine in humans as monitored by a bioassay system based on varicella-zoster virus focus inhibition. J Med Virol. 1987 May;22(1):17-23. PubMed PMID: 3035076.

151: Maudgal PC, De Clercq E, Huyghe P. Experimental thymidine kinase-deficient HSV-1 keratitis: therapeutic attempts. Curr Eye Res. 1987 Apr;6(4):579-84. PubMed PMID: 2953558.

152: Maudgal PC, De Clercq E, Huyghe P. Efficacy of (S)-HPMPA against thymidine kinase-deficient herpes simplex virus-keratitis. Invest Ophthalmol Vis Sci. 1987 Feb;28(2):243-8. PubMed PMID: 8591903.

153: Suzuki S, Machida H, Saneyoshi M. Antiviral activity of various 1-beta-D-arabinofuranosyl-E-5-halogenovinyluracils and E-5-bromovinyl-2'-deoxyuridine against salmon herpes virus, Oncorhynchus masou virus (OMV). Antiviral Res. 1987 Feb;7(2):79-86. PubMed PMID: 3034148.

154: Pepose JS, Biron K. Antiviral sensitivities of the acute retinal necrosis syndrome virus. Curr Eye Res. 1987 Jan;6(1):201-5. PubMed PMID: 3030644.

155: Kit S, Ichimura H, De Clercq E. Phosphorylation of nucleoside analogs by equine herpesvirus type 1 pyrimidine deoxyribonucleoside kinase. Antiviral Res. 1987 Jan;7(1):53-67. PubMed PMID: 3026247.

156: Deeter RG, Khanderia U. Recent advances in antiviral therapy. Clin Pharm. 1986 Dec;5(12):961-76. Review. PubMed PMID: 3542344.

157: Boyd MR, Cole M, Harnden MR, Luk K, Rush MA, Sutton D, Hodge RA. Improvement of the bioavailability of the anti-herpes virus agent BVDU by use of 5'-O-alkoxycarbonyl derivatives with increased metabolic stability. J Antimicrob Chemother. 1986 Oct;18 Suppl B:207-13. PubMed PMID: 3793660.

158: Bird RM, Broadhurst AV, Duncan IB, Hall MJ, Lambert RW, Wong-Kai-In P. Antiviral activity of 5'-PAA and 5'-PFA phosphate esters of 2'-deoxyuridines. J Antimicrob Chemother. 1986 Oct;18 Suppl B:201-5. PubMed PMID: 2947889.

159: Balzarini J, De Clercq E, Verbruggen A, Crumpacker C, Ayusawa D, Seno T. Increased sensitivity of thymidine kinase-deficient (TK-) tumor cell lines to the cell growth inhibitory effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and related compounds. Anticancer Res. 1986 Sep-Oct;6(5):1077-84. PubMed PMID: 2432829.

160: De Clercq E. Potential of bromovinyldeoxyuridine in anticancer chemotherapy. Anticancer Res. 1986 Jul-Aug;6(4):549-56. PubMed PMID: 3752935.

161: Mitchell WL, Ravenscroft P, Hill ML, Knutsen LJ, Judkins BD, Newton RF, Scopes DI. Synthesis and antiviral properties of 5-(2-substituted vinyl)-6-aza-2'-deoxyuridines. J Med Chem. 1986 May;29(5):809-16. PubMed PMID: 3009815.

162: Scheck AC, Wigdahl B, De Clercq E, Rapp F. Prolonged herpes simplex virus latency in vitro after treatment of infected cells with acyclovir and human leukocyte interferon. Antimicrob Agents Chemother. 1986 Apr;29(4):589-93. PubMed PMID: 3010847; PubMed Central PMCID: PMC180447.

163: Baba M, Konno K, Shigeta S, De Clercq E. Inhibitory effects of selected antiviral compounds on newly isolated clinical varicella-zoster virus strains. Tohoku J Exp Med. 1986 Mar;148(3):275-83. PubMed PMID: 3010502.

164: Eggers HJ. [Antiviral chemotherapy]. Monatsschr Kinderheilkd. 1986 Mar;134(3):122-9. German. PubMed PMID: 3010086.

165: De Clercq E, Desgranges C, Herdewijn P, Sim IS, Jones AS, McLean MJ, Walker RT. Synthesis and antiviral activity of (E)-5-(2-bromovinyl)uracil and (E)-5-(2-bromovinyl)uridine. J Med Chem. 1986 Feb;29(2):213-7. PubMed PMID: 3005566.

166: Tricot G, De Clercq E, Boogaerts MA, Verwilghen RL. Oral bromovinyldeoxyuridine therapy for herpes simplex and varicella-zoster virus infections in severely immunosuppressed patients: a preliminary clinical trial. J Med Virol. 1986 Jan;18(1):11-20. PubMed PMID: 3511181.

167: Balzarini J, De Clercq E, Verbruggen A, Ayusawa D, Seno T. Highly selective cytostatic activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine derivatives for murine mammary carcinoma (FM3A) cells transformed with the herpes simplex virus type 1 thymidine kinase gene. Mol Pharmacol. 1985 Dec;28(6):581-7. PubMed PMID: 3001499.

168: Griengl H, Bodenteich M, Hayden W, Wanek E, Streicher W, Stütz P, Bachmayer H, Ghazzouli I, Rosenwirth B. 5-(Haloalkyl)-2'-deoxyuridines: a novel type of potent antiviral nucleoside analogue. J Med Chem. 1985 Nov;28(11):1679-84. PubMed PMID: 4067994.

169: Olofsson S, Lundström M, Datema R. The antiherpes drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) interferes with formation of N-linked and of O-linked oligosaccharides of the herpes simplex virus type 1 glycoprotein C. Virology. 1985 Nov;147(1):201-5. PubMed PMID: 2998063.

170: De Clercq E, Bernaerts R, Balzarini J, Herdewijn P, Verbruggen A. Metabolism of the carbocyclic analogue of (E)-5-(2-iodovinyl)-2'-deoxyuridine in herpes simplex virus-infected cells. Incorporation of C-IVDU into DNA. J Biol Chem. 1985 Sep 5;260(19):10621-8. PubMed PMID: 2993282.

171: Marquardt H, Westendorf J, De Clercq E, Marquardt H. Potent anti-viral 5-(2-bromovinyl) uracil nucleosides are inactive at inducing gene mutations in Salmonella typhimurium and V79 Chinese hamster cells and unscheduled DNA synthesis in primary rat hepatocytes. Carcinogenesis. 1985 Aug;6(8):1207-9. PubMed PMID: 3893787.

172: De Clercq E, Rosenwirth B. Selective in vitro and in vivo activities of 5-(2-haloalkyl)pyrimidine nucleoside analogs, particularly 5-(2-chloroethyl)-2'-deoxyuridine, against herpes simplex virus. Antimicrob Agents Chemother. 1985 Aug;28(2):246-51. PubMed PMID: 3010841; PubMed Central PMCID: PMC180227.

173: Docherty JJ, Trimble JJ, Roman SR, Faulkner SC, Naugle FP, Mundon FK, Zimmerman DH. Lack of oral HSV-2 in a college student population. J Med Virol. 1985 Jul;16(3):283-7. PubMed PMID: 2993498.

174: Balzarini J, de Clercq E, Ayusawa D, Seno T. Murine mammary FM3A carcinoma cells transformed with the herpes simplex virus type 1 thymidine kinase gene are highly sensitive to the growth-inhibitory properties of (E)-5-(2-bromovinyl)-2'-deoxyuridine and related compounds. FEBS Lett. 1985 Jun 3;185(1):95-100. PubMed PMID: 2987041.

175: Perlman ME, Watanabe KA, Schinazi RF, Fox JJ. Nucleosides. 133. Synthesis of 5-alkenyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines and related pyrimidine nucleosides as potential antiviral agents. J Med Chem. 1985 Jun;28(6):741-8. PubMed PMID: 4009596.

176: Freeman DJ, Sacks SL, De Clercq E, Spruance SL. Preclinical assessment of topical treatments of herpes simplex virus infection: 5% (E)-5-(2-bromovinyl)-2'-deoxyuridine cream. Antiviral Res. 1985 Jun;5(3):169-77. PubMed PMID: 2992371.

177: Field HJ. Chemotherapy of Aujeszky's disease (pseudorabies) in the mouse by means of nucleoside analogues: bromovinyldeoxyuridine, acyclovir, and dihydroxypropoxymethylguanine. Antiviral Res. 1985 Jun;5(3):157-68. PubMed PMID: 2992370.

178: Lin JC, Smith MC, Pagano JS. Comparative efficacy and selectivity of some nucleoside analogs against Epstein-Barr virus. Antimicrob Agents Chemother. 1985 Jun;27(6):971-3. PubMed PMID: 2992367; PubMed Central PMCID: PMC180200.

179: Herdewijn P, De Clercq E, Balzarini J, Vanderhaeghe H. Synthesis and antiviral activity of the carbocyclic analogues of (E)-5-(2-halovinyl)-2'-deoxyuridines and (E)-5-(2-halovinyl)-2'-deoxycytidines. J Med Chem. 1985 May;28(5):550-5. PubMed PMID: 2985782.

180: Zhang ZX, Dong WP, Chen HS, Xu ZG, Zhang ZH, Liu SM, De Clercq E. Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on the growth and viral capsid antigen expression of Epstein-Barr virus-associated tumor (B-95-8) cells transplanted to nude mice. Proc Soc Exp Biol Med. 1985 Apr;178(4):616-22. PubMed PMID: 2984692.

181: Zimmerman DH, Mundon FK, Croson SE, Henchal LS, Docherty JJ, O'Neill SP. Identification and typing of herpes simplex virus types 1 and 2 by monoclonal antibodies, sensitivity to the drug (E)-5-(2-bromovinyl)-2'-deoxyuridine, and restriction endonuclease analysis of viral DNA. J Med Virol. 1985 Mar;15(3):215-22. PubMed PMID: 2984324.

182: Swierkosz EM, Arens MQ, Rivetna KA. Problems associated with the use of (E)-5-(2-bromovinyl)-2'-deoxyuridine for typing herpes simplex virus. J Clin Microbiol. 1985 Mar;21(3):459-61. PubMed PMID: 2984249; PubMed Central PMCID: PMC271688.

183: Shigeta S, Yokota T. [Mechanisms of antiherpes drugs and drug resistant virus--effect of BVDU on varicella zoster virus replication]. Rinsho Byori. 1985 Feb;33(2):148-57. Review. Japanese. PubMed PMID: 2987573.

184: Allaudeen HS. Distinctive properties of DNA polymerases induced by herpes simplex virus type-1 and Epstein-Barr virus. Antiviral Res. 1985 Feb;5(1):1-12. PubMed PMID: 2984987.

185: De Clercq E, Balzarini J, Bernaerts R, Herdewijn P, Verbruggen A. Selective antiherpetic activity of carbocyclic analogues of (E)-5-(2-halogenovinyl)-2'-deoxyuridines: dependence on specific phosphorylation by viral thymidine kinase. Biochem Biophys Res Commun. 1985 Jan 16;126(1):397-403. PubMed PMID: 2982373.

186: Benoit Y, Laureys G, Delbeke MJ, De Clercq E. Oral BVDU treatment of varicella and zoster in children with cancer. Eur J Pediatr. 1985 Jan;143(3):198-202. PubMed PMID: 3987714.

187: Lin JC, Smith MC, Choi EI, De Clercq E, Verbruggen A, Pagano JS. Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on replication of Epstein-Barr virus in human lymphoblastoid cell lines. Antiviral Res. 1985;Suppl 1:121-6. PubMed PMID: 3002251.

188: Veerisetty V, Gentry GA. HSV1-specific thymidylate kinase activity in infected cells. Intervirology. 1985;24(1):42-9. PubMed PMID: 2995273.

189: Mayo D, Hilliard J, Landry M, Egbertson S, Mirkovic R. Comparison of four methods for typing low-passage herpes simplex virus isolates. Intervirology. 1985;23(2):112-5. PubMed PMID: 2984142.

190: Samuel J, Knaus EE, Wiebe LI, Tyrrell DL. Synthesis of 131I, 125I and 82Br labelled (E)-5-(2-halovinyl)-2'-deoxyuridines. Int J Appl Radiat Isot. 1984 Nov;35(11):1049-52. PubMed PMID: 6526520.

191: Maudgal PC, De Clercq E, Missotten L. Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections. Antiviral Res. 1984 Oct;4(5):281-91. PubMed PMID: 6335020.

192: Salmon VC, Stanberry LR, Overall JC Jr. More rapid isolation of herpes simplex virus in a continuous line of mink lung cells than in Vero or human fibroblast cells. Diagn Microbiol Infect Dis. 1984 Sep;2(4):317-24. PubMed PMID: 6091988.

193: Yokota T, Konno K, Shigeta S, De Clercq E. Comparative inhibition of DNA polymerases from varicella zoster virus (TK+ and TK-) strains by (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate. Mol Pharmacol. 1984 Sep;26(2):376-80. PubMed PMID: 6090888.

194: Kelly DC. Baculovirus replication: effects of inhibitors of macromolecular synthesis. J Antimicrob Chemother. 1984 Aug;14 Suppl A:43-55. PubMed PMID: 6541648.

195: Sim IS. Oral and topical treatment of experimental HSV-1 genital herpes with (E)-5-(2-bromovinyl)-2'-deoxyuridine. J Antimicrob Chemother. 1984 Aug;14 Suppl A:111-8. PubMed PMID: 6541647.

196: Hantz O, Allaudeen HS, Ooka T, De Clercq E, Trepo C. Inhibition of human and woodchuck hepatitis virus DNA polymerase by the triphosphates of acyclovir, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine and E-5-(2-bromovinyl)-2'-deoxyuridine. Antiviral Res. 1984 Aug;4(4):187-99. PubMed PMID: 6541455.

197: Baba M, Shigeta S, De Clercq E. Influence of various experimental conditions on the inhibitory effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine on varicella-zoster virus replication in cell culture. Tohoku J Exp Med. 1984 Aug;143(4):441-9. PubMed PMID: 6093286.

198: De Clercq E. The antiviral spectrum of (E)-5-(2-bromovinyl)-2'-deoxyuridine. J Antimicrob Chemother. 1984 Aug;14 Suppl A:85-95. Review. PubMed PMID: 6092320.

199: Zou FC, Dutschman GE, De Clercq E, Cheng YC. Differential binding affinities of sugar-modified derivatives of (E)-5-(2-bromovinyl)-2'-deoxyuridine for herpes simplex virus-induced and human cellular deoxythymidine kinases. Biochem Pharmacol. 1984 Jun 1;33(11):1797-800. PubMed PMID: 6329218.

200: Machida H, Sakata S. In vitro and in vivo antiviral activity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and related compounds. Antiviral Res. 1984 Jun;4(3):135-41. PubMed PMID: 6089657.

201: Wildiers J, De Clercq E. Oral (E)-5-(2-bromovinyl)-2'-deoxyuridine treatment of severe herpes zoster in cancer patients. Eur J Cancer Clin Oncol. 1984 Apr;20(4):471-6. PubMed PMID: 6539202.

202: Pavan-Langston D, Park NH, De Clercq E. In vitro effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, 5'-amino-5-iodo-2',5'-dideoxyuridine and 2-deoxy-D-glucose on latent ganglionic herpes simplex virus infection. Antiviral Res. 1984 Apr;4(1-2):53-61. PubMed PMID: 6331305.

203: Field HJ, Anderson JR, Efstathiou S. A quantitative study of the effects of several nucleoside analogues on established herpes encephalitis in mice. J Gen Virol. 1984 Apr;65 ( Pt 4):707-19. PubMed PMID: 6323620.

204: Zhang ZX, Liu YX, Chen HC, Allaudeen HS, De Clercq E. Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on several parameters of Epstein-Barr virus infection. J Gen Virol. 1984 Jan;65 ( Pt 1):37-46. PubMed PMID: 6319572.

205: De Clercq E, Walker RT. Synthesis and antiviral properties of 5-vinylpyrimidine nucleoside analogs. Pharmacol Ther. 1984;26(1):1-44. Review. PubMed PMID: 6099893.

206: Desgranges C, Razaka G, Rabaud M, Bricaud H, Balzarini J, De Clercq E. Phosphorolysis of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and other 5-substituted-2'-deoxyuridines by purified human thymidine phosphorylase and intact blood platelets. Biochem Pharmacol. 1983 Dec 1;32(23):3583-90. PubMed PMID: 6651877.

207: Sacks SL, Teh CZ, Lemchuk-Favel L. Serotyping of herpes simplex virus isolates: a comparison of BVDU sensitivities, indirect immunofluorescence with monoclonal antibodies, and indirect immunofluorescence with cross-adsorbed rabbit antibodies. J Virol Methods. 1983 Oct;7(4):199-206. PubMed PMID: 6317706.

208: Colacino JM, Lopez C. Efficacy and selectivity of some nucleoside analogs as anti-human cytomegalovirus agents. Antimicrob Agents Chemother. 1983 Oct;24(4):505-8. PubMed PMID: 6316843; PubMed Central PMCID: PMC185363.

209: Bubley G, Crumpacker C, De Clercq E, Schnipper L. Effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine on the proliferation of herpes simplex virus type 1-transformed and thymidine kinase-deficient mouse cells. Virology. 1983 Sep;129(2):490-2. PubMed PMID: 6312685.

210: Misra V, Nelson RC, Babiuk LA. Inhibition of glycosylation of bovine herpesvirus 1 glycoproteins by the thymidine analog (E)-5-(2 Bromovinyl)-2'-deoxyuridine. Antimicrob Agents Chemother. 1983 Jun;23(6):857-65. PubMed PMID: 6614891; PubMed Central PMCID: PMC184984.

211: Wang X, Lescott T, De Clercq E, Kelly DC. Baculovirus replication: inhibition of Trichoplusia ni multiple nuclear polyhedrosis virus by [E]-5-(2-bromovinyl)-2'-deoxyuridine. J Gen Virol. 1983 Jun;64 (Pt 6):1221-7. PubMed PMID: 6343553.

212: Kaufman HE, Centifanto-Fitzgerald YM, Varnell ED. Herpes simplex keratitis. Ophthalmology. 1983 Jun;90(6):700-6. PubMed PMID: 6310466.

213: Park NH, Pavan-Langston D, de Clercq E. Efficacy of (E)-5-(2-bromovinyl)-2'-deoxyuridine in the treatment of experimental herpes simplex virus encephalitis in mice. Antiviral Res. 1983 Mar;3(1):7-15. PubMed PMID: 6870230.

214: Zheng ZM, Mayo DR, Hsiung GD. Comparison of biological, biochemical, immunological, and immunochemical techniques for typing herpes simplex virus isolates. J Clin Microbiol. 1983 Mar;17(3):396-9. PubMed PMID: 6302130; PubMed Central PMCID: PMC272653.

215: Shigeta S, Yokota T, Iwabuchi T, Baba M, Konno K, Ogata M, De Clercq E. Comparative efficacy of antiherpes drugs against various strains of varicella-zoster virus. J Infect Dis. 1983 Mar;147(3):576-84. PubMed PMID: 6300257.

216: Larder BA, Cheng YC, Darby G. Characterization of abnormal thymidine kinases induced by drug-resistant strains of herpes simplex virus type 1. J Gen Virol. 1983 Mar;64 Pt 3:523-32. PubMed PMID: 6298344.

217: Larder BA, Derse D, Cheng YC, Darby G. Properties of purified enzymes induced by pathogenic drug-resistant mutants of herpes simplex virus. Evidence for virus variants expressing normal DNA polymerase and altered thymidine kinase. J Biol Chem. 1983 Feb 10;258(3):2027-33. PubMed PMID: 6296119.

218: Sundmacher R. Use of nucleoside analogues in the treatment of herpes simplex virus eye diseases. Metab Pediatr Syst Ophthalmol. 1983;7(2):89-94. PubMed PMID: 6686278.

219: de Clercq E, Zhang ZX, Sim IS. Treatment of experimental herpes simplex virus encephalitis with (E)-5-(2-bromovinyl)-2'-deoxyuridine in mice. Antimicrob Agents Chemother. 1982 Sep;22(3):421-5. PubMed PMID: 7137983; PubMed Central PMCID: PMC183760.

220: Crumpacker CS, Schnipper LE, Kowalsky PN, Sherman DM. Resistance of herpes simplex virus to adenine arabinoside and E-5-(2-bromovinyl)-2'-deoxyuridine: a physical analysis. J Infect Dis. 1982 Aug;146(2):167-72. PubMed PMID: 6286786.

221: Biron KK, Elion GB. Effect of acyclovir combined with other antiherpetic agents on varicella zoster virus in vitro. Am J Med. 1982 Jul 20;73(1A):54-7. PubMed PMID: 6285733.

222: Schinazi RF, Nahmias AJ. Different in vitro effects of dual combinations of anti-herpes simplex virus compounds. Am J Med. 1982 Jul 20;73(1A):40-8. PubMed PMID: 6285731.

223: De Clercq E. Therapeutic potential of BVDU as an antiherpetic drug. Bull Soc Ophtalmol Fr. 1982 Jun-Jul;82(6-7):913. English, French. PubMed PMID: 7172397.

224: Park NH, Pavan-Langston D, Boisjoly HM, De Clercq E. Chemotherapeutic efficacy of E-5-(2-bromovinyl)-2'deoxyuridine for orofacial infection with herpes simplex virus type 1 in mice. J Infect Dis. 1982 Jun;145(6):909-13. PubMed PMID: 6979592.

225: De Clercq E. Comparative efficacy of antiherpes drugs in different cell lines. Antimicrob Agents Chemother. 1982 Apr;21(4):661-3. PubMed PMID: 6282214; PubMed Central PMCID: PMC181961.

226: Mayo DR. Differentiation of herpes simplex virus types 1 and 2 by sensitivity to (E)-5-(2-bromovinyl)-2'-deoxyuridine. J Clin Microbiol. 1982 Apr;15(4):733-6. PubMed PMID: 6279696; PubMed Central PMCID: PMC272176.

227: Honess RW, O'Hare P, Young D. Comparison of thymidine kinase activities indiced in cells productively infected with herpesvirus saimiri and herpes simplex virus. J Gen Virol. 1982 Feb;58(Pt 2):237-49. PubMed PMID: 6278057.

228: De Clercq E, Descamps J, Ogata M, Shigeta S. In vitro susceptibility of varicella-zoster virus to E-5-(2-bromovinyl)-2'-deoxyuridine and related compounds. Antimicrob Agents Chemother. 1982 Jan;21(1):33-8. PubMed PMID: 6282207; PubMed Central PMCID: PMC181824.

229: Cassiman JJ, De Clercq E, Jones AS, Walker RT, Van den Berghe H. Sister chromatid exchange induced by anti-herpes drugs. Br Med J (Clin Res Ed). 1981 Sep 26;283(6295):817-8. PubMed PMID: 6794711; PubMed Central PMCID: PMC1507069.

230: Hettinger ME, Pavan-Langston D, Park NH, Albert DM, De Clercq E, Lin TS. Ac2IDU, BVDU, and thymine arabinoside therapy in experimental herpes keratitis. Arch Ophthalmol. 1981 Sep;99(9):1618-21. PubMed PMID: 7283815.

231: De Clercq E, Zhen-Xi Z, Descamps J, Huygen K. E-5-(2-bromovinyl)-2'-deoxyuridine vs. interferon in the systemic treatment of infection with herpes simplex virus of athymic nude mice. J Infect Dis. 1981 Jun;143(6):846-52. PubMed PMID: 6166694.

232: Maudgal PC, Missotten L, De Clercq E, Descamps J, De Meuter E. Efficacy of (E)-5-(2-bromovinyl)-2'-deoxyuridine in the topical treatment of herpes simplex keratitis. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1981;216(4):261-8. PubMed PMID: 7020469.

233: Maudgal PC, Dralands L, Lamberts L, De Clercq E, Descamps J, Missotten L. Preliminary results of oral BVDU treatment of herpes zoster ophthalmicus. Bull Soc Belge Ophtalmol. 1981;193:49-56. PubMed PMID: 6979370.

234: Maudgal PC, De Clercq E, Descamps J, Missotten L, De Somer P, Busson R, Vanderhaeghe H, Verhelst G, Walker RT, Jones AS. (E)-5-(2-bromovinyl)-2'-Deoxyuridine in the treatment of experimental herpes simplex keratitis. Antimicrob Agents Chemother. 1980 Jan;17(1):8-12. PubMed PMID: 7352751; PubMed Central PMCID: PMC283717.

235: Maudgal PC, De Clercq E, Descamps J, Missotten L. Comparative evaluation of BVDU ((E)-5-(2-bromovinyl)-2'-deoxyuridine) in the treatment of experimental herpes simplex keratitis in rabbits. Bull Soc Belge Ophtalmol. 1979;186:109-18. PubMed PMID: 554711.