Lurtotecan | OSI-211 | CAS#149882-10-0 | topoisomerase I inhibitor

MedKoo Cat#: 205783 | Name: Lurtotecan

Featured

Description:

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

Lurtotecan, also known as OSI-221 and NX-211, is a semisynthetic analogue of camptothecin and a potent topoisomerase I inhibitor. OSI-211 showed potent antileukemia activity in preclinical SCID mouse AML and ALL leukemia models. Lurtotecan 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.

Chemical Structure

Lurtotecan

CAS#149882-10-0 (free base)

Theoretical Analysis

MedKoo Cat#: 205783

Name: Lurtotecan

CAS#: 149882-10-0 (free base)

Chemical Formula: C28H30N4O6

Exact Mass: 518.2165

Molecular Weight: 518.56

Elemental Analysis: C, 64.85; H, 5.83; N, 10.80; O, 18.51

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 1,350.00	2 Weeks
10mg	USD 2,350.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

149882-10-0 (free base) 155773-58-3 (HCl)

Synonym

Lurtotecan; OSI211; OSI 211; OSI-211; NX 211; NX-211; NX211; GI147211; GI-147211; GI 147211; GG211; GG-211; GG 211;

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

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).

HS Tariff Code

2934.99.9001

More Info

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.).

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 518.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

1: Mulholland K, Wu C. Computational Study of Anticancer Drug Resistance Caused by 10 Topisomerase I Mutations, Including 7 Camptothecin Analogs and Lucanthone. J Chem Inf Model. 2016 Sep 26;56(9):1872-83. doi: 10.1021/acs.jcim.6b00317. Epub 2016 Sep 1. PMID: 27564845. 2: Oostendorp RL, van de Steeg E, van der Kruijssen CM, Beijnen JH, Kenworthy KE, Schinkel AH, Schellens JH. Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors. Drug Metab Dispos. 2009 Apr;37(4):917-23. doi: 10.1124/dmd.108.024901. Epub 2009 Jan 12. PMID: 19139163. 3: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Dec;27(10):711-38. PMID: 16395422. 4: Glaberman U, Rabinowitz I, Verschraegen CF. Alternative administration of camptothecin analogues. Expert Opin Drug Deliv. 2005 Mar;2(2):323-33. doi: 10.1517/17425247.2.2.323. PMID: 16296757. 5: Takimoto CH. Are there any better camptothecins than the ones we have? Clin Adv Hematol Oncol. 2003 Oct;1(10):578-9, 600. PMID: 16258452. 6: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Jul-Aug;27(6):411-61. PMID: 16179960. 7: 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. doi: 10.1200/JCO.2005.02.028. Epub 2005 Feb 7. PMID: 15699482. 8: 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. doi: 10.1016/j.ejca.2004.08.024. PMID: 15571957. 9: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612. PMID: 15538546. 10: Kuppens IE, Beijnen J, Schellens JH. Topoisomerase I inhibitors in the treatment of gastrointestinal cancer: from intravenous to oral administration. Clin Colorectal Cancer. 2004 Sep;4(3):163-80. doi: 10.3816/ccc.2004.n.017. PMID: 15377400. 11: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jun;26(5):357-91. PMID: 15319815. 12: Gelmon K, Hirte H, Fisher B, Walsh W, Ptaszynski M, Hamilton M, Onetto N, Eisenhauer E. A phase 1 study of OSI-211 given as an intravenous infusion days 1, 2, and 3 every three weeks in patients with solid cancers. Invest New Drugs. 2004 Aug;22(3):263-75. doi: 10.1023/B:DRUG.0000026252.86842.e2. PMID: 15122073. 13: 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. doi: 10.1016/j.ygyno.2003.12.037. PMID: 15047241. 14: 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. doi: 10.1002/cncr.20132. PMID: 15042679. 15: MacKenzie MJ, Hirte HW, Siu LL, Gelmon K, Ptaszynski M, Fisher B, Eisenhauer E. A phase I study of OSI-211 and cisplatin as intravenous infusions given on days 1, 2 and 3 every 3 weeks in patients with solid cancers. Ann Oncol. 2004 Apr;15(4):665-70. doi: 10.1093/annonc/mdh133. PMID: 15033677. 16: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):483-506. PMID: 12949633. 17: Tomkinson B, Bendele R, Giles FJ, Brown E, Gray A, Hart K, LeRay JD, Meyer D, Pelanne M, Emerson DL. OSI-211, a novel liposomal topoisomerase I inhibitor, is active in SCID mouse models of human AML and ALL. Leuk Res. 2003 Nov;27(11):1039-50. doi: 10.1016/s0145-2126(03)00092-4. PMID: 12859997. 18: Lansiaux A, Bailly C. Symphonie pour camptothécines [A symphony for the camptothecins]. Bull Cancer. 2003 Mar;90(3):239-45. French. PMID: 12801826. 19: Ulukan H, Swaan PW. Camptothecins: a review of their chemotherapeutic potential. Drugs. 2002;62(14):2039-57. doi: 10.2165/00003495-200262140-00004. PMID: 12269849. 20: 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. doi: 10.1023/a:1014454821885. PMID: 12003197.