| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
Topoisomerase I Topoisomerase II
The primary targets of Intoplicine dimesylate are DNA topoisomerase I and II. These enzymes are essential for DNA replication and transcription, as they manage DNA supercoiling and topology. By inhibiting both topoisomerase I and II, Intoplicine dimesylate disrupts the DNA relaxation process necessary for cellular proliferation. The compound also strongly binds to DNA with an association constant (K_A) of 2 x 10⁵ /M, which contributes to its mechanism of action by stabilizing the enzyme-DNA complex and leading to DNA damage and cell death. |
|---|---|
| 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].
In vitro, Intoplicine dimesylate exhibits high antitumor activity. It strongly binds DNA, thereby increasing the length of linear DNA. Its mechanism of action involves the inhibition of DNA topoisomerase I and II, leading to the disruption of DNA replication and transcription in cancer cells. The compound's cytotoxicity is a result of its ability to stabilize the cleavable complex formed by topoisomerases and DNA, ultimately triggering cell death pathways. |
| 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].
In vivo, Intoplicine dimesylate has demonstrated significant antitumor efficacy. It 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, with a total dose of 36 mg/kg. This indicates a potent ability to inhibit tumor growth in animal models. The compound's in vivo activity is attributed to its dual inhibition of topoisomerase I and II, which effectively halts the proliferation of cancer cells. |
| Enzyme Assay |
In vitro enzyme/receptor binding studies for Intoplicine dimesylate focus on its interaction with DNA and topoisomerases. The compound's ability to inhibit topoisomerase I and II can be assessed using standard enzymatic assays that measure the relaxation of supercoiled DNA. Its strong binding to DNA (K_A = 2 x 10⁵ /M) can be evaluated using techniques such as surface plasmon resonance or fluorescence spectroscopy. These assays help characterize the compound's mechanism of action and its potency as a topoisomerase inhibitor.
|
| Cell Assay |
In vitro cell-based assays for Intoplicine dimesylate evaluate its antiproliferative effects on various cancer cell lines. Cells are treated with the compound, and cell viability is measured using standard assays such as MTT or CellTiter-Glo. The compound's cytotoxicity is determined by calculating the IC₅₀ values. The mechanism of cell death, such as apoptosis, can be investigated by assessing markers like caspase activation or DNA fragmentation.
|
| Animal Protocol |
In vivo animal studies for Intoplicine dimesylate are conducted in xenograft mouse models. Tumor-bearing mice are treated with the compound, and tumor growth inhibition is monitored. The highest non-toxic dosage (HNTD) of 6 mg/kg/injection, total dose of 36 mg/kg, has been used to assess its efficacy. Endpoints include tumor volume, tumor weight, and survival. Pharmacodynamic analysis may include assessment of topoisomerase inhibition and DNA damage in tumor tissues.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Intoplicine dimesylate have been characterized in preclinical studies. The compound is typically administered via injection in animal models. Its molecular weight is 540.65 g/mol. The compound is soluble in DMSO and water. For research use, it is stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years. Further details on its half-life, clearance, and bioavailability are available from the primary research literature.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Intoplicine dimesylate has been evaluated in preclinical studies. The highest non-toxic dosage (HNTD) has been established at 6 mg/kg/injection in animal models. As a DNA topoisomerase inhibitor, its potential toxicities may include bone marrow suppression and gastrointestinal effects, which are common to this class of anticancer agents. The compound is for research use only and is not intended for human therapeutic applications.
|
| References |
|
| Additional Infomation |
Additional information: Intoplicine dimesylate is also known as RP 60475 dimesylate. Its molecular formula is C₂₃H₃₂N₄O₇S₂. The compound is a potent DNA topoisomerase I and II inhibitor with strong DNA binding affinity. It has demonstrated high antitumor activity in preclinical models. This product is for research use only and is not approved for clinical or therapeutic applications.
|
| 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)
|
| 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. View More
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. |
| 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.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
