| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
TP-300 targets DNA topoisomerase I through its active metabolite CH-0793076 (TP3076). The metabolite binds to the topoisomerase I-DNA complex and prevents religation of the single-strand break, stabilizing the cleavable complex. This leads to collision with the replication fork, generation of double-strand breaks, and induction of apoptosis in cancer cells.
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|---|---|
| ln Vitro |
TP3076, or CH0793076, demonstrated antiproliferative action against PC-6/BCRP and PC-6/pRC cells for six days at 37°C, with IC50 values of 0.18 nM and 0.35 nM, respectively [1].
In vitro, TP-300 and its active metabolite TP3076 exhibit potent cytotoxic activity against various cancer cell lines, including colorectal and gastric cancer lines. TP3076 inhibits topoisomerase I activity with high potency and induces DNA damage and apoptosis. The prodrug TP-300 is converted to TP3076 in the presence of plasma esterases and at acidic pH, demonstrating pH-dependent activation. |
| ln Vivo |
The nine models (WiDr, HT-29, NCI-H460 and AsPC-1, HCT116, COLO 201, HCT-15, Calu-6, and NCI-N87) with BCRP expression showed greater than 50% tumor growth inhibition when the water-soluble prodrug TP300 of CH0793076 (1-100 mg/kg; intravenous bolus once weekly for three weeks for three doses) was administered [1].
In vivo, TP-300 has demonstrated antitumor activity in xenograft models of colorectal and gastric cancer. After intravenous administration, it is converted to the active metabolite TP3076, which achieves high systemic exposure and tumor penetration. It inhibits tumor growth and is investigated for its potential in treating solid malignancies. |
| Enzyme Assay |
The in vitro topoisomerase I inhibition assay for TP-300 uses the active metabolite TP3076. The assay uses recombinant topoisomerase I, supercoiled DNA, and ATP. The compound is incubated with the enzyme and DNA, and relaxation or cleavage products are analyzed by agarose gel electrophoresis. DNA cleavage is quantified by measuring linear DNA formation.
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| Cell Assay |
In vitro cell experiments with TP-300 use colorectal cancer (HCT116, SW620) and gastric cancer (MKN45) cell lines. Cells are treated with TP-300 or its active metabolite TP3076, and cell viability is measured by MTT or SRB assay. DNA damage is assessed by comet assay or γ-H2AX immunostaining, and apoptosis is evaluated by flow cytometry.
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| Animal Protocol |
In vivo animal experiments with TP-300 use xenograft models in immunodeficient mice. TP-300 is administered intravenously, and tumor growth inhibition is measured. Pharmacokinetic studies determine plasma concentrations of TP-300 and its active metabolite TP3076. Tumor tissue is analyzed for topoisomerase I inhibition and DNA damage markers.
|
| References |
| Molecular Formula |
C26H26N4O4
|
|---|---|
| Molecular Weight |
458.509
|
| Exact Mass |
458.195
|
| CAS # |
534605-78-2
|
| Related CAS # |
CH-0793076 TFA;2740278-76-4
|
| PubChem CID |
9981577
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
1.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
34
|
| Complexity |
989
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CCCCCN1C=NC2=CC=CC3=C2C1=C4CN5C(=CC6=C(C5=O)COC(=O)[C@@]6(CC)O)C4=N3
|
| InChi Key |
NPAAFPODGAKMTC-SANMLTNESA-N
|
| InChi Code |
InChI=1S/C26H26N4O4/c1-3-5-6-10-29-14-27-18-8-7-9-19-21(18)23(29)15-12-30-20(22(15)28-19)11-17-16(24(30)31)13-34-25(32)26(17,33)4-2/h7-9,11,14,33H,3-6,10,12-13H2,1-2H3/t26-/m0/s1
|
| Chemical Name |
(10S)-10-ethyl-10-hydroxy-23-pentyl-8-oxa-4,15,21,23-tetrazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16(24),17,19,21-octaene-5,9-dione
|
| Synonyms |
TP300; TP 300; TP-300
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1810 mL | 10.9049 mL | 21.8098 mL | |
| 5 mM | 0.4362 mL | 2.1810 mL | 4.3620 mL | |
| 10 mM | 0.2181 mL | 1.0905 mL | 2.1810 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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