Indotecan (LMP400; NSC724998) is a novel, potent and selective topoisomerase I inhibitor with IC50 values of 300, 1200, 560 nM for P388, HCT116, MCF-7 cell lines, respectively. It is undergoing Phase I trials and may have anticancer activity. Inhibitors of human nuclear type IB topoisomerase (Top1) are potent and commonly used anticancer drugs.

Physicochemical Properties

Molecular Formula	C26H26N2O7
Molecular Weight	478.493847370148
Exact Mass	478.174
Elemental Analysis	C, 65.26; H, 5.48; N, 5.85; O, 23.41
CAS #	915303-09-2
Related CAS #	915303-09-2 (Indotecan; LMP-400); 915360-05-3 ( Indimitecan, LMP776)
PubChem CID	11533060
Appearance	White to gray solid powder
LogP	2.619
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	6
Heavy Atom Count	35
Complexity	872
Defined Atom Stereocenter Count	0
SMILES	O=C1C2C3C(C(N(C=2C2C1=CC1=C(C=2)OCO1)CCCN1CCOCC1)=O)=CC(OC)=C(OC)C=3
InChi Key	FMFIFGLHVOZDEL-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H26N2O7/c1-31-19-10-15-18(13-20(19)32-2)26(30)28(5-3-4-27-6-8-33-9-7-27)24-16-11-21-22(35-14-34-21)12-17(16)25(29)23(15)24/h10-13H,3-9,14H2,1-2H3
Chemical Name	15,16-dimethoxy-20-(3-morpholin-4-ylpropyl)-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	NSC-724998; NSC724998; NSC 724998; LMP-400; LMP400; LMP 400; Indotecan
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.
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	Topoisomerase I
ln Vitro	The Indotecan IC50 values for L. inhibition (48 hours). It was 0.10 μM, 0.10 μM, and 57.16 μM for fantum promastigotes, isolated infected splenocytes, and uninfected splenocytes, respectively [2]. 30 minutes) inhibits L. DNA synthesis and creates covalent complexes of TopI-DNA. infantum cultures [2].
ln Vivo	The livers of mice with visceral leishmaniasis and their own livers are less parasitized when indocean (2.5 mg/kg; intraperitoneally every 2 days for 15 days) is administered [2].
Animal Protocol	Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (4-6 weeks) were injected intravenously (iv) (iv)(iv) with posterior circulating parasites through the tail vein [2] Doses: 2.5 mg/kg per injection Body weight Route of Administration: intraperitoneal (ip) injection once every 2 days for a total of 15 days (8 doses total) Experimental Results: A dramatic reduction in the number of transformed amastigotes recovered from target organs of drug-treated animals was observed.
References	[1]. Indotecan (LMP400) and AM13-55: two novel indenoisoquinolines show potential for treating visceral leishmaniasis. Antimicrob Agents Chemother. 2012 Oct;56(10):5264-70. [2]. Single-Molecule Supercoil Relaxation Assay as a Screening Tool to Determine the Mechanism and Efficacy of Human Topoisomerase IB Inhibitors. Mol Cancer Ther. 2015 Nov;14(11):2552-9.

Solubility Data

Solubility (In Vitro)

DMSO: < 1 mg/mL

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	2.0899 mL	10.4495 mL	20.8991 mL
	5 mM	0.4180 mL	2.0899 mL	4.1798 mL
	10 mM	0.2090 mL	1.0450 mL	2.0899 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.