| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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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.
| Targets |
Topoisomerase I
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|---|---|
| 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].
In U-CH1 chordoma cells, rubitecan inhibited cell viability with an IC50 of 0.32 ± 0.04 μM (efficacy >50%). In U-CH2 cells, the IC50 was 0.83 ± 0.21 μM with only 17% maximal inhibition. In non-neoplastic CCL4 cells, the IC50 was 7.7 μM with 27% inhibition. [4] Combination treatment: When U-CH2 cells were exposed to bortezomib in the presence of 500 nM rubitecan, the potency of bortezomib improved significantly: bortezomib IC50 decreased from 3.93 μM (alone) to 68.6 nM (P=0.036). [4] In primary chordoma cell cultures (C24, C25, C32), combining bortezomib with rubitecan also enhanced bortezomib’s potency by an average of 2- to 9-fold compared to bortezomib alone. [4] |
| ln Vivo |
In a human pancreatic tumor xenograft model (CFPAC-1 carcinoma inoculated into mice), administration of rubitecan for 5 days per week for 4 weeks resulted in a dose-dependent decrease in mean tumor volume out to 64 days, with no tumor regrowth observed at the highest dose of 2.0 mg/kg/day [1].
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| Cell Assay |
Cell viability was measured using a luciferase-coupled ATP quantitation assay (CellTiter-Glo). Cells were suspended in culture medium and dispensed at 500-1000 cells per well in 1536-well white/solid-bottom plates. After overnight incubation at 37°C, compounds at multiple concentrations were added via pin tool (23 nL per well). Final compound concentrations in 5 μL assay volume ranged from 0.6 nM to 46 μM. Plates were incubated for 48 h at 37°C, followed by addition of CellTiter-Glo reagent (5 μL per well). After 30 min incubation at room temperature, luminescence was measured. For combination studies, cells were treated with bortezomib in the presence of a fixed concentration of rubitecan (500 nM) for 48 h. [4]
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| Animal Protocol |
Mice were inoculated with human pancreatic CFPAC-1 carcinoma cells. Rubitecan was administered for 5 days per week for 4 weeks. The highest dose tested was 2.0 mg/kg/day, which led to no tumor regrowth and a dose-dependent reduction in mean tumor volume lasting up to 64 days [1].
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| ADME/Pharmacokinetics |
Rubitecan is a water-insoluble camptothecin derivative formulated as an oral agent. Its antitumor activity depends on delivery of the molecule in its intact lactone form; when hydrolyzed to the carboxylate form under neutral or basic conditions, rubitecan has little antitumor activity. Oral administration with an acidic beverage (e.g., orange juice, cola) has shown activity in clinical trials [1].
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| Toxicity/Toxicokinetics |
In a phase II trial of 58 heavily pretreated patients with advanced pancreatic cancer receiving oral rubitecan at a starting dose of 1.5 mg/m²/day for 5 consecutive days per week, the most common nonhematologic adverse events were: asthenia (45%, grade 3: 21%), nausea (62%, grade 3: 12%), vomiting (59%, grade 3: 14%), diarrhea (40%, grade 3: 9%), anorexia (33%), abdominal pain (29%, grade 3: 9%), dehydration (26%, grade 3: 12%, grade 4: 2%), and alopecia (14%, grade 3: 2%). Cystitis occurred in only 1 patient (2%) with increased hydration (≥3 liters/day). Hematologic toxicities included: grade 3/4 leukopenia (26%), grade 3/4 neutropenia (21%), grade 3/4 thrombocytopenia (10%), and grade 3 anemia (12%). Only 3 patients (5%) discontinued treatment due to adverse events as the primary reason. Dose delays or reductions were required in 40% of patients, mainly due to hematologic or gastrointestinal toxicities. All deaths were related to disease progression; however, in one patient, dehydration and kidney failure (probably related to study drug) may have been contributing factors [1].
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| References |
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| Additional Infomation |
Rubitecan is a pyranoindoquinoline compound, a derivative of camptothecin with its 9th hydrogen atom replaced by a nitro group. It is a prodrug of 9-aminocamptothecin. It has antitumor activity and is an EC 5.99.1.2 (DNA topoisomerase) inhibitor and prodrug. It is a pyranoindoquinoline compound, a C-nitro compound, a semi-synthetic derivative, a tertiary alcohol, and a δ-lactone. Rubitecan is a semi-synthetic drug associated with camptothecin with potent antitumor and antiviral properties. Rubitecan binds to and inhibits topoisomerase I, inducing single-strand breaks in protein-linked DNA, thereby blocking DNA and RNA synthesis in dividing cells; the drug also prevents the repair of reversible single-strand DNA breaks. (NCI04)
Drug Indications Studied for the treatment of pancreatic cancer, leukemia (unspecified), melanoma, ovarian cancer, and cancer/tumor (unspecified). Mechanism of Action Rubitecan interferes with tumor growth by preventing DNA from unwinding during replication through DNA topoisomerase 1. Rubitecan (9-nitro-20(S)-camptothecin) is an orally active topoisomerase I inhibitor with broad antitumor activity in human xenograft models. In prior phase II studies in pancreatic cancer, objective response rates of 15-29% were reported. In the current phase II trial in patients with locally advanced or metastatic pancreatic cancer refractory to prior chemotherapy, oral rubitecan produced a 7% partial response rate and 16% disease stabilization rate (23% overall response plus stabilization) as confirmed by independent radiology review. Median survival was 3 months for the overall cohort and 10 months for responding patients. The recommended starting dose is 1.5 mg/m²/day orally for 5 consecutive days per week, with dose adjustments based on toxicity. Hydration to at least 3 liters/day is recommended to reduce cystitis risk [1]. |
| Molecular Formula |
C20H15N3O6
|
|---|---|
| Molecular Weight |
393.35
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| Exact Mass |
393.096
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| Elemental Analysis |
C, 61.07; H, 3.84; N, 10.68; O, 24.40
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| CAS # |
91421-42-0
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| PubChem CID |
472335
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
816.3±65.0 °C at 760 mmHg
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| Melting Point |
182-186ºC
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| Flash Point |
447.5±34.3 °C
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| Vapour Pressure |
0.0±3.1 mmHg at 25°C
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| Index of Refraction |
1.762
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| LogP |
1.38
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
29
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| Complexity |
861
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C2COC([C@](C=2C=C2C3N=C4C=CC=C(C4=CC=3CN12)[N+](=O)[O-])(O)CC)=O
|
| InChi Key |
VHXNKPBCCMUMSW-FQEVSTJZSA-N
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| 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
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| 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
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| Synonyms |
9-nitro-camptothecin; RFS-2000; RFS2000; RFS 2000; 9NC; nitrocamptothecin; 9-nitro-CPT; trade names: Camptogen; Orathecin
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 58~62.5 mg/mL (147.5~158.9 mM)
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|---|---|
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00005872 | Completed | Drug: rubitecan | Lung Cancer | Astex Pharmaceuticals, Inc. | May 1999 | Phase 2 |
| NCT00006230 | Completed | Drug: rubitecan | Ovarian Cancer | European Organisation for Research and Treatment of Cancer - EORTC |
May 2000 | Phase 2 |
| NCT00006082 | Completed | Drug: rubitecan | Lung Cancer | European Organisation for Research and Treatment of Cancer - EORTC |
May 2000 | Phase 2 |
| NCT00006026 | Completed | Drug: rubitecan | Bladder Cancer Urethral Cancer |
European Organisation for Research and Treatment of Cancer - EORTC |
May 2000 | Phase 2 |
| NCT00005826 | Completed | Drug: rubitecan | Brain and Central Nervous System Tumors |
European Organisation for Research and Treatment of Cancer - EORTC |
March 2000 | Phase 2 |
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