Rubitecan (RFS-2000), a semisynthetic camptothecin analog, is an orally bioactive topoisomerase I inhibitor antitumor and antiviral activity. It inhibits DNA and RNA synthesis in dividing cells, induces protein-linked DNA single-strand breaks, and binds to topoisomerase I. prevents reversible single-strand DNA breaks from being repaired as well.

Physicochemical Properties

Molecular Formula	C20H15N3O6
Molecular Weight	393.35
Exact Mass	393.096
Elemental Analysis	C, 61.07; H, 3.84; N, 10.68; O, 24.40
CAS #	91421-42-0
PubChem CID	472335
Appearance	Light yellow to yellow solid powder
Density	1.6±0.1 g/cm3
Boiling Point	816.3±65.0 °C at 760 mmHg
Melting Point	182-186ºC
Flash Point	447.5±34.3 °C
Vapour Pressure	0.0±3.1 mmHg at 25°C
Index of Refraction	1.762
LogP	1.38
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	1
Heavy Atom Count	29
Complexity	861
Defined Atom Stereocenter Count	1
SMILES	O=C1C2COC([C@](C=2C=C2C3N=C4C=CC=C(C4=CC=3CN12)[N+](=O)[O-])(O)CC)=O
InChi Key	VHXNKPBCCMUMSW-FQEVSTJZSA-N
InChi Code	InChI=1S/C20H15N3O6/c1-2-20(26)13-7-16-17-10(8-22(16)18(24)12(13)9-29-19(20)25)6-11-14(21-17)4-3-5-15(11)23(27)28/h3-7,26H,2,8-9H2,1H3/t20-/m0/s1
Chemical Name	(19S)-19-ethyl-19-hydroxy-8-nitro-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
Synonyms	9-nitro-camptothecin; RFS-2000; RFS2000; RFS 2000; 9NC; nitrocamptothecin; 9-nitro-CPT; trade names: Camptogen; Orathecin
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	Topoisomerase I
ln Vitro	Rubitecan (RFS 2000) suppresses CCL4, U-CH1, and U-CH2 cells with IC50 values of 7.7 µM, 0.83, and 0.32 µM, respectively[4].
References	[1]. Phase II trial of oral rubitecan in previously treated pancreatic cancer patients. Oncologist. 2005 Mar;10(3):183-90. [2]. Rubitecan: 9-NC, 9-Nitro-20(S)-camptothecin, 9-nitro-camptothecin, 9-nitrocamptothecin, RFS 2000, RFS2000. Drugs R D. 2004;5(5):305-11. [3]. Rubitecan. [4]. Identification of repurposed small molecule drugs for chordoma therapy. Cancer Biol Ther. 2013 Jul;14(7):638-47.
Additional Infomation	Rubitecan is a pyranoindolizinoquinoline that is camptothecin in which the hydrogen at position 9 has been replaced by a nitro group. It is a prodrug for 9-aminocamptothecin. It has a role as an antineoplastic agent, an EC 5.99.1.2 (DNA topoisomerase) inhibitor and a prodrug. It is a pyranoindolizinoquinoline, a C-nitro compound, a semisynthetic derivative, a tertiary alcohol and a delta-lactone. Rubitecan is a semisynthetic agent related to camptothecin with potent antitumor and antiviral properties. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks. (NCI04) Drug Indication Investigated for use/treatment in pancreatic cancer, leukemia (unspecified), melanoma, ovarian cancer, and cancer/tumors (unspecified). Mechanism of Action Rubitecan prevents DNA from unwinding during replication via DNA topoisomerase 1, therefore interfering with tumor growth.

Solubility Data

Solubility (In Vitro)

DMSO: 58~62.5 mg/mL (147.5~158.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5423 mL	12.7113 mL	25.4227 mL
	5 mM	0.5085 mL	2.5423 mL	5.0845 mL
	10 mM	0.2542 mL	1.2711 mL	2.5423 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.