Intoplicine (RP 60475) dimesylate, an antitumor analogue of the 7H benzo[e]pyrido[4,3-b]indole series, is a DNA topoisomerase I and II inhibitor. Intoplicine dimesylate binds strongly to DNA (KA = 2 x 105 /M), thereby increasing the length of linear DNA.

Physicochemical Properties

Molecular Formula	C23H32N4O7S2
Molecular Weight	540.65
Exact Mass	540.171
CAS #	133711-99-6
Related CAS #	Intoplicine;125974-72-3
PubChem CID	3086634
Appearance	Light blue to blue solid powder
LogP	4.838
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	36
Complexity	566
Defined Atom Stereocenter Count	0
InChi Key	JAUYMMJDKJISLX-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H24N4O.2CH4O3S/c1-13-12-23-21(22-9-4-10-25(2)3)19-18-16-7-6-15(26)11-14(16)5-8-17(18)24-20(13)19;2*1-5(2,3)4/h5-8,11-12,24,26H,4,9-10H2,1-3H3,(H,22,23);2*1H3,(H,2,3,4)
Chemical Name	16-[3-(dimethylamino)propylamino]-13-methyl-11,15-diazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),3,5,8,12(17),13,15-octaen-5-ol;methanesulfonic acid
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)

Biological Activity

Targets	Topoisomerase I Topoisomerase II
ln Vitro	After being exposed to Intoplicine dimesylate for one hour at final concentrations of 2.5 and 10.0 micrograms/mL, respectively, 26% and 54% of the assessable specimens exhibited positive in vitro responses[2]. Positive reactions were observed in 16% and 71% of the assessable specimens after continuous exposure to Intoplicine dimesylate at doses of 0.25 micrograms/mL and 2.5 micrograms/mL, respectively[2]. At 10.0 micrograms/mL of Intoplicine dimesylate, colony-forming units of breast (71%), non-small-cell lung (69%), and ovarian (45%) cancer are seen to be active[2].
ln Vivo	Intoplicine dimesylate exhibits high activity with a T/C of 0% and a matching total log cell death of 3 at the highest non-toxic dosage (HNTD) of 6 mg/kg/injection, total dose, 36 mg/kg[3].
References	[1]. Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities. Cancer Res. 1993;53(24):5987-5993. [2]. Activity of intoplicine (RP60475), a new DNA topoisomerase I and II inhibitor, against human tumor colony-forming units in vitro. J Natl Cancer Inst. 1994;86(1):30-33. [3]. Antitumor activity of intoplicine (RP 60475, NSC 645008), a new benzo-pyrido-indole: evaluation against solid tumors and leukemias in mice. Invest New Drugs. 1993;11(4):263-277.

Solubility Data

Solubility (In Vitro)

DMSO : 115 mg/mL (212.71 mM) H2O : 100 mg/mL (184.96 mM)x

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5.75 mg/mL (10.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5.75 mg/mL (10.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 5.75 mg/mL (10.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8496 mL	9.2481 mL	18.4963 mL
	5 mM	0.3699 mL	1.8496 mL	3.6993 mL
	10 mM	0.1850 mL	0.9248 mL	1.8496 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.