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Elinafide

Description of Elinafide (LU 79553): LU 79553 is a novel bis-naphthalimide which is highly cytotoxic in vitro with EC50 (concentration required for 50% inhibition of growth) ranging from 2 x 10(-7) to 5 x 10(-10) M. A number of studies were conducted to examine its antitumor activity in human xenograft models. Complete regression of MX-1 (mammary carcinoma) xenografts was observed when LU 79553 was administered i.v. daily for 5 doses at 20 mg/kg (2 cycles starting on Days 6 and 20) or every 3 days for 2 doses at 55 mg/kg (2 cycles starting on Days 6 and 13) or every 7 days for 4 doses. Complete regression was also seen in the MX-1 model when tumors were staged at 1-2 g prior to the initiation of treatment. Regressions (complete or partial) were observed in the LX-1 (lung), CX-1 (colon), DLD (colon), and LOX (melanoma) xenograft models. A significant increase in the median survival time of OVCAR-3- (ovarian carcinoma) bearing mice was noted in LU 79553-treated animals (treated/control = 195%).  (source: Cancer Res. 1995 Mar 1;55(5):1176-80.)

Current developer:  Abbott Laboratories and Genzyme

LU 79553 is a novel bis-naphthalimide which is highly cytotoxic in vitro with EC50 (concentration required for 50% inhibition of growth) ranging from 2 x 10(-7) to 5 x 10(-10) M. A number of studies were conducted to examine its antitumor activity in human xenograft models.  Complete regression of MX-1 (mammary carcinoma) xenografts was observed when LU 79553 was administered i.v. daily for 5 doses at 20 mg/kg (2 cycles starting on Days 6 and 20) or every 3 days for 2 doses at 55 mg/kg (2 cycles starting on Days 6 and 13) or every 7 days for 4 doses. Complete regression was also seen in the MX-1 model when tumors were staged at 1-2 g prior to the initiation of treatment. Regressions (complete or partial) were observed in the LX-1 (lung), CX-1 (colon), DLD (colon), and LOX (melanoma) xenograft models. A significant increase in the median survival time of OVCAR-3- (ovarian carcinoma) bearing mice was noted in LU 79553-treated animals (treated/control = 195%). The excellent activity of this compound in such a wide variety of tumor types suggests LU 79553 merits further investigation in clinical trials. see: http://www.ncbi.nlm.nih.gov/pubmed/7867004.

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10: Awada A, Thödtmann R, Piccart MJ, Wanders J, Schrijvers AH, Von Broen IM, Hanauske AR; EORTC-ECSG phase I study. An EORTC-ECSG phase I study of LU 79553 administered every 21 or 42 days in patients with solid tumours. Eur J Cancer. 2003 Apr;39(6):742-7. PubMed PMID: 12651198.

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13: Gallego J, Reid BR. Solution structure and dynamics of a complex between DNA and the antitumor bisnaphthalimide LU-79553: intercalated ring flipping on the millisecond time scale. Biochemistry. 1999 Nov 16;38(46):15104-15. PubMed PMID: 10563793.

14: Amato AA, Kagan-Hallet K, Jackson CE, Lampkin S, Wolfe GI, Ferrante M, Bigio EH, Barohn RJ. The wide spectrum of myofibrillar myopathy suggests a multifactorial etiology and pathogenesis. Neurology. 1998 Dec;51(6):1646-55. PubMed PMID: 9855517.

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16: Bailly C, Braña M, Waring MJ. Sequence-selective intercalation of antitumour bis-naphthalimides into DNA. Evidence for an approach via the major groove. Eur J Biochem. 1996 Aug 15;240(1):195-208. PubMed PMID: 8797854.

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18: Bousquet PF, Braña MF, Conlon D, Fitzgerald KM, Perron D, Cocchiaro C, Miller R, Moran M, George J, Qian XD, et al. Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. Cancer Res. 1995 Mar 1;55(5):1176-80. PubMed PMID: 7867004.