LMP744 (Mj-III-65, NSC-706744) is a novel and potent DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity. LMP744 can overcome multidrug resistance and forms persistent topoisomerase I cleavage complexes. Protein-linked DNA breaks were found in cells treated with nanomolar concentrations of LMP744, which is consistent with Top1 poisoning. LMP744 was found to be cytotoxic in studies conducted on human cells cultured. Additionally, camptothecin-resistant cell lines showed some degree of cross-resistance. Moreover, LMP744 has antitumor activity in tumor xenografts from mice.

Physicochemical Properties

Molecular Formula	C24H24N2O7
Molecular Weight	452.45656
Exact Mass	452.158
Elemental Analysis	C, 63.71; H, 5.35; N, 6.19; O, 24.75
CAS #	308246-52-8
Related CAS #	LMP744 hydrochloride;308246-57-3
PubChem CID	397888
Appearance	Brown to dark brown solid powder
LogP	2.321
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	33
Complexity	802
Defined Atom Stereocenter Count	0
SMILES	OCCNCCCN1C2=C(C(C3=CC(OCO4)=C4C=C23)=O)C5=CC(OC)=C(OC)C=C5C1=O
InChi Key	QCSDJDQOJBQTDV-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H24N2O7/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,3-7,12H2,1-2H3
Chemical Name	20-[3-(2-hydroxyethylamino)propyl]-15,16-dimethoxy-5,7-dioxa-20-azapentacyclo[10.8.0.02,10.04,8.013,18]icosa-1(12),2,4(8),9,13,15,17-heptaene-11,19-dione
Synonyms	LMP744; LMP-744; LMP 744; Mj-III-65; MJ-III65; MJ-III 65; NSC 706744; NSC-706744; NSC-706744
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
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

Targets	Top1
ln Vitro	LMP744 (MJ-III-65) has a GI50 value of 0.1 μM for NCI60 cells[2]. LMP744 (0.1–5 μM, 3 days) causes a dose-dependent accumulation of cells in the S and G2 phases of the cell cycle[2].
ln Vivo	LMP744 (MJ-III65) (10-50 mg/kg) moderately active against human A253 and FaDu tumor xenografts without significant toxicity when given intraperitoneally (i.v.) once a week for four weeks in nude mice[1].
Cell Assay	Cell Line: P388 and P388 Top1-deficient murine leukemia cells Concentration: 0.1-100 μM Incubation Time: 3 days Result: Induced dose-dependent accumulation of cells in the S and G2 phases of the cell cycle.
Animal Protocol	Athymic nude mice (nu/nu, female, 20-25 g, 8-12 weeks old) transplanted with A253 and FaDu human head and neck xenografts[1]. 10, 25, or 50 mg/kg/week, 4 weeks I.V. push via tail vein
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]. Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance. Cancer Res. 2007 Nov 1;67(21):10397-405.
Additional Infomation	Topoisomerase-1 Inhibitor LMP744 is an indenoisoquinoline derivative and topoisomerase 1 (Top1) inhibitor, with potential antineoplastic activity. Upon administration, LMP744 binds to and stabilizes cleaved DNA-Top1 complexes, which prevents DNA re-ligation, induces stable, irreversible DNA strand breaks, prevents DNA repair, and leads to cell cycle arrest and apoptosis. As tumor cells proliferate at a much higher rate than normal cells, LMP744 specifically targets cancer cells. Top1, a DNA modifying enzyme essential for transcription, replication, and repair of double-strand DNA breaks, is overexpressed in tumor cells.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 4.17 mg/mL (~9.2 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	2.2101 mL	11.0507 mL	22.1014 mL
	5 mM	0.4420 mL	2.2101 mL	4.4203 mL
	10 mM	0.2210 mL	1.1051 mL	2.2101 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.