| Size | Price | Stock | Qty |
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| 5mg |
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Purity: ≥98%
| Targets |
The primary target of TH-1318 is topoisomerase I, a nuclear enzyme that relieves torsional stress in DNA during replication and transcription. As a camptothecin derivative, TH-1318 stabilizes the topoisomerase I-DNA cleavage complex, preventing the religation of the DNA strand and leading to the accumulation of DNA breaks. This DNA damage triggers cell cycle arrest and apoptosis. The compound's 7-ethyl-14-amino substitution pattern on the pentacyclic core is designed to enhance its pharmacological properties, including oral bioavailability and blood-brain barrier penetration. TH-1318 is not a substrate for major efflux pumps (MDR1, MRP1, and BCRP), which is a key advantage over other camptothecins that are often subject to efflux-mediated resistance. This property contributes to the compound's improved brain exposure and its efficacy against tumors that overexpress these efflux pumps. By targeting topoisomerase I and overcoming drug resistance mechanisms, TH-1318 offers a promising approach for the treatment of various cancers, including those of the central nervous system.
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| ln Vitro |
When given orally to mice, TH1338 (compound 3b) demonstrates considerable brain penetration [1]. Compound 3b, TH1338, demonstrates strong anticancer efficacy in the human tumor xenograft model H460 (NSCLC) [1].
In vitro, TH-1318 demonstrates excellent cytotoxic potency against human tumor cell lines. As a camptothecin derivative, it stabilizes the topoisomerase I-DNA cleavage complex, leading to DNA damage and apoptosis. The compound exhibits significant cytotoxicity and blood-brain barrier penetration in cellular models. Its in vitro activity is well-characterized and forms the basis for its use in cancer research. TH-1318's ability to overcome efflux pump-mediated resistance is a key feature of its in vitro activity. The compound's potency against various cancer cell lines, including those that are resistant to other camptothecins, makes it a valuable tool for studying topoisomerase I inhibitors and for developing new therapeutic strategies. |
| ln Vivo |
In vivo, TH-1318 demonstrates excellent anti-tumor activity following oral administration. The compound is orally bioavailable and CNS-penetrant, making it suitable for the treatment of brain tumors and brain metastases. In mouse xenograft models of human tumors, TH-1318 has been shown to inhibit tumor growth and improve survival. The compound's ability to cross the blood-brain barrier is a key advantage for its use in treating brain tumors. Its oral bioavailability allows for convenient administration in preclinical studies. The compound's in vivo efficacy is attributed to its potent topoisomerase I inhibition and its ability to overcome drug resistance mechanisms. Further studies are needed to fully characterize the compound's in vivo pharmacokinetics and efficacy in different cancer models.
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| Enzyme Assay |
Cell-free topoisomerase I assays with TH-1318 are performed using purified human topoisomerase I and plasmid DNA. The compound is incubated with the enzyme and DNA, and DNA cleavage products are analyzed by agarose gel electrophoresis to determine topoisomerase I inhibition. These cell-free assays are essential for characterizing the potency of TH-1318 as a topoisomerase I inhibitor. The compound's activity is compared with other camptothecin derivatives to assess its relative potency. The cell-free assay data provide a quantitative measure of the compound's inhibitory activity and are used to guide the design of more potent and selective inhibitors. The results from cell-free assays are complemented by cellular and in vivo studies to provide a comprehensive picture of the compound's biological activity.
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| Cell Assay |
Cell viability assay[1]
Cell Types: H460 (NSCLC) human tumor xenograft model. Tested Concentrations: 40 mg/kg. Incubation period: oral administration. Experimental Results: demonstrated excellent anti-tumor activity. In cellular assays, human tumor cell lines (e.g., various cancer types) are treated with TH-1318 at varying concentrations. Cell viability is assessed using MTT or CellTiter-Glo assays. Cytotoxicity IC50 values are determined. Apoptosis and DNA damage markers are evaluated by flow cytometry and Western blot. The compound's effects on cell cycle progression are also assessed. These cellular assays are crucial for understanding the functional consequences of topoisomerase I inhibition and for validating the compound's activity as a camptothecin derivative. The compound's potency in cellular systems is consistent with its activity in cell-free assays. The results from these assays provide valuable information for the use of TH-1318 in cancer research. |
| Animal Protocol |
In vivo efficacy of TH-1318 is evaluated in mouse xenograft models of human tumors. The compound is administered orally. Tumor growth inhibition, animal survival, and brain penetration of the compound are monitored. The compound's ability to cross the blood-brain barrier is a key measure of its efficacy in brain tumor models. These in vivo studies are essential for confirming the compound's efficacy in a physiologically relevant context and for guiding the development of TH-1318 as a therapeutic agent for brain tumors and other cancers.
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| ADME/Pharmacokinetics |
TH-1318 is orally bioavailable and exhibits significant blood-brain barrier penetration. It is not a substrate for major efflux pumps (MDR1, MRP1, BCRP), resulting in improved brain exposure. Standard PK parameters are determined in preclinical studies. The compound's oral bioavailability and brain penetration are key advantages for its therapeutic use. The pharmacokinetic data obtained from these studies are essential for designing appropriate dosing regimens and for interpreting the results of efficacy and toxicity studies.
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| Toxicity/Toxicokinetics |
Toxicological evaluation includes assessment of the compound's safety profile in animal models. As a camptothecin derivative, potential toxicities include myelosuppression and gastrointestinal effects. Standard toxicology studies evaluate organ toxicity and therapeutic window. The compound's safety profile is established through these studies, and the no-observed-adverse-effect level (NOAEL) is determined. The compound is for research use only and has not been evaluated for human safety. Standard safety precautions should be followed when handling TH-1318, including the use of appropriate personal protective equipment and adherence to institutional safety guidelines.
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| References |
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| Additional Infomation |
TH-1318 (TH1338, CAS 1258494-60-8) is a research compound for laboratory use only. It is an orally active derivative of camptothecin with potential anti-cancer activity. The compound exhibits significant blood-brain barrier penetration and cytotoxicity. It is designed to overcome MDR1/MRP1/BCRP efflux. TH-1318 is not approved for human therapeutic use and is intended for research purposes only. It should be stored according to the manufacturer's recommendations, typically at -20°C, to ensure stability. When handling TH-1318, researchers should follow standard safety protocols for handling chemical reagents, including the use of appropriate personal protective equipment and working in a well-ventilated area.
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| Molecular Formula |
C22H21N3O4
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| Molecular Weight |
391.43
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| Exact Mass |
391.153
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| CAS # |
1258494-60-8
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| Related CAS # |
1258494-60-8;
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| PubChem CID |
53318291
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.805
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
29
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| Complexity |
834
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC1=C2CN3C(=C(C4=C(C3=O)COC(=O)[C@@]4(CC)O)N)C2=NC5=CC=CC=C51
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| InChi Key |
GDSWDKUWTYXXOX-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C22H21N3O4/c1-3-11-12-7-5-6-8-15(12)24-18-13(11)9-25-19(18)17(23)16-14(20(25)26)10-29-21(27)22(16,28)4-2/h5-8,28H,3-4,9-10,23H2,1-2H3/t22-/m0/s1
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| Chemical Name |
(S)-5-Amino-4,11-diethyl-4-hydroxy-1,12-dihydro-14H-pyrano[3',4'
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| Synonyms |
TH1318 TH 1318 TH-1318.
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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 : ~10 mg/mL (~25.55 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.82 mg/mL (4.65 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 18.2 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5547 mL | 12.7737 mL | 25.5474 mL | |
| 5 mM | 0.5109 mL | 2.5547 mL | 5.1095 mL | |
| 10 mM | 0.2555 mL | 1.2774 mL | 2.5547 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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