Lurtotecan

• CAT Number: M094308
• CAS Number: 149882-10-0
• Molecular Formula: C28H30N4O6
• Molecular Weight: 518.57
• Purity: ≥95%
• Storage: Store at -20°C
• InChI: InChI=1S/C28H30N4O6/c1-3-28(35)20-11-22-25-18(14-32(22)26(33)19(20)15-38-27(28)34)17(13-31-6-4-30(2)5-7-31)16-10-23-24(12-21(16)29-25)37-9-8-36-23/h10-12,35H,3-9,13-15H2,1-2H3/t28-/m0/s1
• InChIKey: RVFGKBWWUQOIOU-NDEPHWFRSA-N
• SMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC6=C(C=C5N=C4C3=C2)OCCO6)CN7CCN(CC7)C)O

Liposomal lurtotecan is a liposome-encapsulated formulation of lurtotecan with antineoplastic activity. Lurtotecan, a semisynthetic analogue of camptothecin, selectively stabilizes the topoisomerase I-DNA covalent complex and forms an enzyme-drug-DNA ternary complex during S phase of the cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-stranded DNA breaks. This ultimately results in an inhibition of DNA replication, inducing double-stranded DNA breakages, obstruction of RNA and protein synthesis and triggering apoptosis. Furthermore, this agent also stimulates degradation of topoisomerase I, likely mediated through ubiquitin-proteasomal pathway. Liposomal delivery of lurtotecan improves its penetration and delivery into tumors while lowering systemic side effects. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Reference

1:Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group. Dark GG, Calvert AH, Grimshaw R, Poole C, Swenerton K, Kaye S, Coleman R, Jayson G, Le T, Ellard S, Trudeau M, Vasey P, Hamilton M, Cameron T, Barrett E, Walsh W, McIntosh L, Eisenhauer EA.J Clin Oncol. 2005 Mar 20;23(9):1859-66. Epub 2005 Feb 7. PMID: 15699482 2:Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study. Duffaud F, Borner M, Chollet P, Vermorken JB, Bloch J, Degardin M, Rolland F, Dittrich C, Baron B, Lacombe D, Fumoleau P; EORTC-New Drug Development Group/New Drug Development Program..Eur J Cancer. 2004 Dec;40(18):2748-52. PMID: 15571957 3:A phase II study of liposomal lurtotecan (OSI-211) in patients with topotecan resistant ovarian cancer. Seiden MV, Muggia F, Astrow A, Matulonis U, Campos S, Roche M, Sivret J, Rusk J, Barrett E.Gynecol Oncol. 2004 Apr;93(1):229-32. PMID: 15047241 4:Phase I and pharmacokinetic study of a low-clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia. Giles FJ, Tallman MS, Garcia-Manero G, Cortes JE, Thomas DA, Wierda WG, Verstovsek S, Hamilton M, Barrett E, Albitar M, Kantarjian HM.Cancer. 2004 Apr 1;100(7):1449-58. PMID: 15042679 Free Article5:Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studies. Schellens JH, Heinrich B, Lehnert M, Gore ME, Kaye SB, Dombernowsky P, Paridaens R, van Oosterom AT, Verweij J, Loos WJ, Calvert H, Pavlidis N, Cortes-Funes H, Wanders J, Roelvink M, Sessa C, Selinger K, Wissel PS, Gamucci T, Hanauske AR.Invest New Drugs. 2002 Feb;20(1):83-93. PMID: 12003197 6:Structural identification and biological activity of 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin, a photodegradant of lurtotecan. Loos WJ, Verweij J, Kehrer DF, de Bruijn P, de Groot FM, Hamilton M, Nooter K, Stoter G, Sparreboom A.Clin Cancer Res. 2002 Mar;8(3):856-62. PMID: 11895919 Free Article7:Phase I and pharmacologic study of liposomal lurtotecan, NX 211: urinary excretion predicts hematologic toxicity. Kehrer DF, Bos AM, Verweij J, Groen HJ, Loos WJ, Sparreboom A, de Jonge MJ, Hamilton M, Cameron T, de Vries EG.J Clin Oncol. 2002 Mar 1;20(5):1222-31. PMID: 11870164 8:Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice. Desjardins JP, Abbott EA, Emerson DL, Tomkinson BE, Leray JD, Brown EN, Hamilton M, Dihel L, Ptaszynski M, Bendele RA, Richardson FC.Anticancer Drugs. 2001 Mar;12(3):235-45. PMID: 11290871 9:Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan. Emerson DL, Bendele R, Brown E, Chiang S, Desjardins JP, Dihel LC, Gill SC, Hamilton M, LeRay JD, Moon-McDermott L, Moynihan K, Richardson FC, Tomkinson B, Luzzio MJ, Baccanari D.Clin Cancer Res. 2000 Jul;6(7):2903-12. PMID: 10914740 Free Article10:Liposomal lurtotecan (NX211): determination of total drug levels in human plasma and urine by reversed-phase high-performance liquid chromatography. Loos WJ, Kehrer D, Brouwer E, Verweij J, de Bruijn P, Hamilton M, Gill S, Nooter K, Stoter G, Sparreboom A.J Chromatogr B Biomed Sci Appl. 2000 Jan 28;738(1):155-63. PMID: 10778937