| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
Lurtotecan targets DNA topoisomerase I (TOP1). It selectively stabilizes the topoisomerase I-DNA covalent complex, forming an enzyme-drug-DNA ternary complex during the S phase of the cell cycle.
|
|---|---|
| ln Vitro |
Lurtotecan potently inhibits topoisomerase I-mediated DNA religation, leading to the accumulation of single-strand breaks. This ultimately results in the inhibition of DNA replication, induction of double-strand DNA breaks, obstruction of RNA and protein synthesis, and triggering of apoptosis. The agent also stimulates the degradation of topoisomerase I, likely through the ubiquitin-proteasomal pathway.
|
| ln Vivo |
OSI-211 demonstrated potent antileukemia activity in preclinical SCID mouse models of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Liposomal delivery of lurtotecan improves its penetration and delivery into tumors while lowering systemic side effects.
|
| Enzyme Assay |
In vitro enzyme assays typically involve measuring the ability of lurtotecan to inhibit the religation activity of topoisomerase I. The compound is incubated with purified topoisomerase I and a DNA substrate, and the stabilization of the cleavable complex is assessed by gel electrophoresis or using a DNA relaxation assay. IC50 values are determined by quantifying the inhibition of enzyme activity across a range of compound concentrations.
|
| Cell Assay |
In vitro cellular assays evaluate the antiproliferative effects of lurtotecan using cancer cell lines. Cells are cultured in appropriate medium and treated with varying concentrations of the compound for 48-72 hours. Cell viability is assessed using assays such as MTT, CCK-8, or ATP-lite. The IC50 is calculated from dose-response curves. Cell cycle analysis by flow cytometry and apoptosis detection via Annexin V staining are also commonly performed.
|
| Animal Protocol |
In vivo efficacy studies are conducted in mouse xenograft models bearing human tumor cells. Lurtotecan is administered intravenously, often in a liposomal formulation, at various dose levels and schedules. Tumor growth inhibition is monitored by caliper measurements, and endpoints include tumor volume, time to progression, and survival. Pharmacodynamic markers such as TOP1 cleavage complex formation are assessed in tumor tissues.
|
| ADME/Pharmacokinetics |
Lurtotecan has a molecular weight of 518.56 and a logP of 1.474. The compound is soluble in DMSO but not in water. Liposomal encapsulation significantly alters its pharmacokinetic profile, improving tumor penetration and circulation time while reducing systemic toxicity. In clinical trials, liposomal lurtotecan was administered via intravenous infusion.
|
| Toxicity/Toxicokinetics |
In preclinical studies, liposomal lurtotecan demonstrated an improved safety profile compared to the free drug, with reduced systemic side effects. Common toxicities associated with topoisomerase I inhibitors include myelosuppression and gastrointestinal effects. The compound was generally well-tolerated in clinical trials, though it was ultimately discontinued for its indicated use.
|
| References |
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.
|
| Additional Infomation |
Lurtotecan is being investigated in the clinical trial NCT00022594 (Liposome Lurtotecan for the treatment of patients with metastatic or locally recurrent head and neck cancer). Lurtotecan is a semi-synthetic camptothecin analog with antitumor activity. Lurtotecan selectively stabilizes the topoisomerase I-DNA covalent complex, forming an enzyme-drug-DNA ternary complex. Due to the formation of this complex, the initial cleavage and rejoining steps are inhibited, followed by replication fork collisions with broken DNA strands, leading to DNA replication inhibition, double-strand DNA breaks, and triggering apoptosis. In addition to inhibiting DNA replication, Lurtotecan also inhibits RNA synthesis, polyubiquitination and degradation of topoisomerase I, and chromatin reorganization.
Lurtotecan was under investigation in clinical trial NCT00022594 for metastatic or locally recurrent head and neck cancer. Its liposomal formulation (liposomal lurtotecan) was developed to enhance drug delivery and reduce toxicity. The compound is also known by synonyms OSI-211, NX-211, GI147211, and GG211. It has a chemical formula of C28H30N4O6. |
| Molecular Formula |
C28H30N4O6
|
|---|---|
| Molecular Weight |
518.561
|
| Exact Mass |
518.217
|
| CAS # |
149882-10-0
|
| Related CAS # |
149882-10-0;155773-58-3 (HCl);
|
| PubChem CID |
60956
|
| Appearance |
White to yellow solid powder
|
| Density |
1.5g/cm3
|
| Boiling Point |
844.8ºC at 760mmHg
|
| Flash Point |
464.7ºC
|
| Vapour Pressure |
2.51E-30mmHg at 25°C
|
| Index of Refraction |
1.73
|
| LogP |
1.474
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
38
|
| Complexity |
1070
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC6=C(C=C5N=C4C3=C2)OCCO6)CN7CCN(CC7)C)O
|
| 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
|
| Chemical Name |
(18S)-18-ethyl-18-hydroxy-2-[(4-methylpiperazin-1-yl)methyl]-6,9,20-trioxa-13,24-diazahexacyclo[12.11.0.03,12.05,10.015,24.017,22]pentacosa-1,3,5(10),11,13,15,17(22)-heptaene-19,23-dione
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~4.33 mg/mL (~8.35 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9284 mL | 9.6421 mL | 19.2842 mL | |
| 5 mM | 0.3857 mL | 1.9284 mL | 3.8568 mL | |
| 10 mM | 0.1928 mL | 0.9642 mL | 1.9284 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
