Lurtotecan

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205783

CAS#: 149882-10-0

Description: 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)


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10mg
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25mg
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2g
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50mg
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500mg
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5g
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Lurtotecan is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205783
Name: Lurtotecan
CAS#: 149882-10-0
Chemical Formula: C28H30N4O6
Exact Mass: 518.21653
Molecular Weight: 518.561
Elemental Analysis: C, 64.85; H, 5.83; N, 10.80; O, 18.51


Synonym: Lurtotecan; OSI221; OSI 221; OSI-221; NX 211; NX-211; NX211.

IUPAC/Chemical Name: (S)-8-ethyl-8-hydroxy-15-((4-methylpiperazin-1-yl)methyl)-11,14-dihydro-2H-[1,4]dioxino[2,3-g]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-9,12(3H,8H)-dione

InChi Key: RVFGKBWWUQOIOU-NDEPHWFRSA-N

InChi Code: 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

SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(CN5CCN(C)CC5)C6=CC(OCCO7)=C7C=C6N=C4C3=C2)=O


Technical Data

Appearance:
Solid powder

Purity:
>98%

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Phase II study of lurtotecan: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION:  The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B. (source: J Clin Oncol. 2005 Mar 20;23(9):1859-66. )
  
Phase II study of lurtotecan: From July 2001 to March 2002, 32 patients from 14 institutions were enrolled in the "within" arm and 18 in the "outside" arm. In the "within" arm, two patients were ineligible because their tumour site was not allowed in the protocol (nasopharynx, skin) and two other patients never started treatment. Of the 46 eligible patients who started treatment, there was one objective response (response rate: 2.2% (95% Confidence Interval (CI): [0-11.5%]). Twelve patients in the "within" arm and 6 in the "outside" arm had stable disease, with a median duration of 18 weeks, 95% CI (12.7-25.7). The median time to progression was 6 weeks (95%CI: [5.9-12.7] weeks). Haematological toxicity was moderate in both arms. The most common haematological toxicity was grade 1-2 anaemia in 79% of patients. Non-haematological toxicity was mild in both arms. The most common grade 3-4 non-haematological toxicity was infection in 8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN. (source: Eur J Cancer. 2004 Dec;40(18):2748-52.).
 
 


References

1: 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. 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. J Clin Oncol. 2005 Mar 20;23(9):1859-66. Epub 2005 Feb 7. PubMed PMID: 15699482.

2: 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. 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. Eur J Cancer. 2004 Dec;40(18):2748-52. PubMed PMID: 15571957.

3: Seiden MV, Muggia F, Astrow A, Matulonis U, Campos S, Roche M, Sivret J, Rusk J, Barrett E. A phase II study of liposomal lurtotecan (OSI-211) in patients with topotecan resistant ovarian cancer. Gynecol Oncol. 2004 Apr;93(1):229-32. PubMed PMID: 15047241.

4: Giles FJ, Tallman MS, Garcia-Manero G, Cortes JE, Thomas DA, Wierda WG, Verstovsek S, Hamilton M, Barrett E, Albitar M, Kantarjian HM. Phase I and pharmacokinetic study of a low-clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia. Cancer. 2004 Apr 1;100(7):1449-58. PubMed PMID: 15042679.

5: 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. Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studies. Invest New Drugs. 2002 Feb;20(1):83-93. PubMed PMID: 12003197.

6: Loos WJ, Verweij J, Kehrer DF, de Bruijn P, de Groot FM, Hamilton M, Nooter K, Stoter G, Sparreboom A. Structural identification and biological activity of 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin, a photodegradant of lurtotecan. Clin Cancer Res. 2002 Mar;8(3):856-62. PubMed PMID: 11895919.

7: Kehrer DF, Bos AM, Verweij J, Groen HJ, Loos WJ, Sparreboom A, de Jonge MJ, Hamilton M, Cameron T, de Vries EG. Phase I and pharmacologic study of liposomal lurtotecan, NX 211: urinary excretion predicts hematologic toxicity. J Clin Oncol. 2002 Mar 1;20(5):1222-31. PubMed PMID: 11870164.

8: Desjardins JP, Abbott EA, Emerson DL, Tomkinson BE, Leray JD, Brown EN, Hamilton M, Dihel L, Ptaszynski M, Bendele RA, Richardson FC. Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice. Anticancer Drugs. 2001 Mar;12(3):235-45. PubMed PMID: 11290871.

9: 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. Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan. Clin Cancer Res. 2000 Jul;6(7):2903-12. PubMed PMID: 10914740.

10: Loos WJ, Kehrer D, Brouwer E, Verweij J, de Bruijn P, Hamilton M, Gill S, Nooter K, Stoter G, Sparreboom A. Liposomal lurtotecan (NX211): determination of total drug levels in human plasma and urine by reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 2000 Jan 28;738(1):155-63. PubMed PMID: 10778937.