LMP744 HCl (Mj-III65, NSC706744; Mj-III-65, NSC-706744), the hydrochloride salt of LMP744, is a DNA intercalator and Topoisomerase I (Top1) inhibitor with anticancer activity. LMP744 produces persistent topoisomerase I cleavage complexes and can overcome multidrug resistance. Consistent with Top1 poisoning, protein-linked DNA breaks were detected in cells treated with LMP744 at nanomolar concentrations. Studies in human cells in culture found LMP744 to be cytotoxic. Furthermore, limited cross-resistance was observed in camptothecin-resistant cell lines. LMP744 also exhibits antitumor activity in mouse tumor xenografts.
Physicochemical Properties
| Molecular Formula | C24H25CLN2O7 |
| Molecular Weight | 488.92 |
| Exact Mass | 488.135 |
| CAS # | 308246-57-3 |
| Related CAS # | LMP744;308246-52-8 |
| PubChem CID | 397887 |
| Appearance | Light brown to brown solid powder |
| LogP | 3.123 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 34 |
| Complexity | 802 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | POXWLZDVWCKKEX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C24H24N2O7.ClH/c1-30-17-8-13-16(11-18(17)31-2)24(29)26(6-3-4-25-5-7-27)22-14-9-19-20(33-12-32-19)10-15(14)23(28)21(13)22/h8-11,25,27H,3-7,12H2,1-2H31H |
| Chemical Name | 6-(3-((2-hydroxyethyl)amino)propyl)-2,3-dimethoxy-5H-[1,3]dioxolo[4',5' |
| Synonyms | Mj-III65, NSC706744Mj-III-65, NSC-706744 LMP744 HCl LMP 744 HCl |
| 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, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | LMP744 (MJ-III-65) has a GI50 value of 0.1 μM for NCI60 cells[2]. In the S and G2 phases of the cell cycle, dose-dependent cell accumulation is induced by LMP744 (0.1–5 μM, 3 days) [2]. |
| ln Vivo | When given as a weekly intravenous bolus for four weeks in nude mice, LMP744 (MJ-III-65) (10-50 mg/kg) exhibits moderate effectiveness against human A253 and FaDu tumor xenografts with no obvious harm [1]. |
| Cell Assay |
Cytotoxicity assay[2] Cell Types: P388 and P388 Top1-deficient mouse leukemia cells. Tested Concentrations: 0.1-100 μM Incubation Duration: 3 days Experimental Results: Induces dose-dependent accumulation of cells in S and G2 phases of the cell cycle. |
| Animal Protocol |
Animal/Disease Models: Athymic nude mice (nu/nu, female, 20-25 g, 8-12 weeks old) were transplanted with A253 and FaDu human head and neck xenografts [1]. Doses: 10, 25, or 50 mg/kg/week, 4 weeks Route of Administration: intravenous (iv) (iv)bolus injection via tail vein Experimental Results: Moderate activity against human A253 and FaDu tumor xenografts with no significant toxicity. |
| References |
[1]. Cellular topoisomerase I inhibition and antiproliferative activity by MJ-III-65 (NSC 706744), an indenoisoquinoline topoisomerase I poison. Mol Pharmacol. 2005 Feb;67(2):523-30. [2]. Bisindenoisoquinoline bis-1,3-{( 5,6-dihydro-5,11-diketo-11H-indeno [1,2-c]isoquinoline)-6-propylamino}propane bis(trifluoroacetate) (NSC 727357), a DNA intercalator and topoisomerase inhibitor with antitumor activity. Mol Pharmacol. 2006. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~105 mg/mL (~214.76 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0453 mL | 10.2266 mL | 20.4532 mL | |
| 5 mM | 0.4091 mL | 2.0453 mL | 4.0906 mL | |
| 10 mM | 0.2045 mL | 1.0227 mL | 2.0453 mL |