| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Intoplicine inhibits activities of both topoisomerase I and II via intercalating into the DNA helix. By intercalating, it hinders the movements of enzymes along DNA molecules during DNA transcription and replication. It stabilizes the ternary cleavable complex, leading to DNA double-strand breaks and cell death. This dual inhibition allows it to overcome resistance to single-target topoisomerase inhibitors.
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| ln Vitro |
When treated to Intoplicine for 1 hour at final doses of 2.5 μg/mL and 10.0 μg/mL, 26% and 54% of evaluable samples showed a positive in vitro response, respectively [2]. During continuous exposure to Intoplicine at doses of 0.25 μg/mL and 2.5 μg/mL, 16% and 71% of evaluable samples showed positive reactions, respectively [2]. Activity against breast (71%), non-small cell lung cancer (69%), and ovarian cancer (45%) cancer colony-forming units was seen after 1 hour of exposure to Intoplicine at a dosage of 10.0 μg/mL [2].
In vitro, Intoplicine shows its activity through inhibition of DNA topoisomerase I and II. It is the most active analogue evaluated in the 7H-benzo[e]-pyrido-[4,3-b]-indole series of antineoplastic compounds. It retains full activity in camptothecin-resistant and m-AMSA-resistant cell lines and shows incomplete cross-resistance with doxorubicin, cisplatin, and etoposide. |
| ln Vivo |
At the highest nontoxic dose (HNTD) (6 mg/kg/injection, total dose 36 mg/kg), Intoplicine demonstrated high activity with a T/C of 0%, equating to a total log cell death of 3[ 3].
In vivo, Intoplicine achieved complete tumor regression (T/C=0%) in murine colon, pancreatic, and breast cancer xenograft models. Its broad antitumor activity and ability to overcome drug resistance made it a promising candidate for clinical development. |
| Enzyme Assay |
Topoisomerase I and II inhibition is assessed using DNA relaxation and supercoiling assays. Purified enzymes are incubated with supercoiled plasmid DNA in the presence of varying concentrations of Intoplicine. The extent of DNA relaxation or supercoiling is analyzed by agarose gel electrophoresis to determine the compound's inhibitory potency.
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| Cell Assay |
Antiproliferative activity is evaluated using a panel of human cancer cell lines. Cells are treated with Intoplicine, and cell viability is measured. The concentration causing 50% growth inhibition (GI50) is calculated for each cell line.
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| Animal Protocol |
Antitumor efficacy is evaluated in mice bearing human tumor xenografts. Intoplicine is administered intravenously, and tumor volume is measured over time. Tumor growth inhibition (TGI) is calculated by comparing the treatment group to the control group.
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| ADME/Pharmacokinetics |
Intoplicine has a validated Phase II dose of 270 mg/m², administered as a 1-hour IV infusion every three weeks. It exhibits linear pharmacokinetics, enabling efficient translational study design. Its clearance and half-life are consistent with other topoisomerase inhibitors.
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| Toxicity/Toxicokinetics |
Based on its mechanism of DNA damage, potential toxicities include myelosuppression (decreased blood cell counts), gastrointestinal effects (nausea, vomiting, diarrhea), and other effects associated with DNA-damaging agents. As a dual topoisomerase inhibitor, it may also cause more pronounced bone marrow suppression.
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| References |
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| Additional Infomation |
Intoplicine is a pyridoindole compound. Intoplicine has been used in clinical trials for the treatment of undetermined adult solid tumors according to specific protocols. Intoplicine is a benzopyridoindole derivative with antitumor activity. It inhibits the activity of topoisomerases I and II by intercalating into the DNA double helix, thereby hindering the movement of these enzymes along the DNA molecule during transcription and replication, respectively. Furthermore, the drug stabilizes the DNA-enzyme complex during topoisomerase unwinding, leading to double-strand and single-strand DNA breaks. Therefore, these effects inhibit tumor cell growth and induce apoptosis.
Intoplicine is a research compound that was investigated in Phase I/II clinical trials for the treatment of various cancers. Its dual topoisomerase I and II inhibition and ability to overcome resistance made it a promising candidate. It serves as a valuable tool for studying topoisomerase biology and for developing new anticancer agents that can overcome drug resistance. |
| Molecular Formula |
C21H24N4O
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|---|---|
| Molecular Weight |
348.45
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| Exact Mass |
348.195
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| CAS # |
125974-72-3
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| Related CAS # |
Intoplicine dimesylate;133711-99-6
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| PubChem CID |
65954
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| Appearance |
White to off-white solid powder
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| Density |
1.286g/cm3
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| Boiling Point |
635.5ºC at 760mmHg
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| Flash Point |
338.2ºC
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| Vapour Pressure |
9.55E-17mmHg at 25°C
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| Index of Refraction |
1.755
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| LogP |
4.319
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
473
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
QROONAIPJKQFMC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24N4O/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/h5-8,11-12,24,26H,4,9-10H2,1-3H3,(H,22,23)
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| 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
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| Synonyms |
RP-60475; NSC-D-645008; Intoplicine
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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 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)
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| Solubility (In Vitro) |
DMSO : ~80 mg/mL (~229.59 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (5.74 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 20.0 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: ≥ 2 mg/mL (5.74 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 20.0 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. View More
Solubility in Formulation 3: ≥ 2 mg/mL (5.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8699 mL | 14.3493 mL | 28.6985 mL | |
| 5 mM | 0.5740 mL | 2.8699 mL | 5.7397 mL | |
| 10 mM | 0.2870 mL | 1.4349 mL | 2.8699 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.
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