Simmitecan
Simmitecan is a potent topoisomerase I (TOP1) inhibitor, which is a 9-substituted lipophilic camptothecin (Camptothecin (HY-16560)) derivative. Simmitecan blocks DNA replication and transcription, thereby inducing tumor cell apoptosis by inhibiting the activity of TOP1. Simmitecan can be used in the research of cancers such as liver cancer.
For research use only. We do not sell to patients.
- CAS No.: 951290-31-6
- Formula: C34H38N4O6
- Molecular Weight:598.70
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[1]|
Top1 |
CYP3A4 8.95 μM (IC50) |
CYP2D6 32.9 μM (IC50) |
In Vitro
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | Cmax | AUC0-24 | T1/2 | MRT | CLplasma | Vss |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 15 mg/kg | i.v. | 5124 nM | 8142 nM·h | 0.95 h | 1.14 h | 3.16 L/h/kg | 3.57 L/kg |
| Rat[1] | 3.75 mg/kg | i.v. | 1651 nM | 3709 nM·h | 1.45 h | 1.85 h | 1.82 L/h/kg | 3.34 L/kg |
| Rat[1] | 7.5 mg/kg | i.v. | 3518 nM | 8922 nM·h | 1.46 h | 1.92 h | 1.54 L/h/kg | 2.91 L/kg |
| Rat[1] | 15 mg/kg | i.v. | 7192 nM | 17906 nM·h | 1.42 h | 1.91 h | 1.51 L/h/kg | 2.86 L/kg |
| Dog[1] | 1.25 mg/kg | i.v. | 616 nM | 2050 nM·h | 1.95 h | 2.74 h | 1.12 L/h/kg | 3.03 L/kg |
| Dog[1] | 2.5 mg/kg | i.v. | 1135 nM | 3712 nM·h | 1.90 h | 2.74 h | 1.20 L/h/kg | 3.27 L/kg |
| Dog[1] | 5 mg/kg | i.v. | 2101 nM | 6417 nM·h | 1.72 h | 2.45 h | 1.46 L/h/kg | 3.54 L/kg |
In Vivo
Simmitecan (15 mg/kg; intravenous injection; single administration; 8 h) exhibits extensive distribution in tissues including tumors and substantial conversion into its active metabolite L-2-Z in nude mouse xenograft models bearing the human hepatocellular carcinoma SMMC-7721 cell line[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male and female, 250-300 g)[1]
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Dosage:3.75 mg/kg; 7.5 mg/kg; 15 mg/kg
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Administration:i.v.; single dose; 48 h
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Result:Was rapidly biotransformed into its active metabolite L-2-Z in vivo and extensively distributed in most tissues (with the highest concentrations observed in the pancreas, kidneys, and liver).
Was predominantly eliminated via biliary excretion, and metabolism was also a major elimination route for the intact drug after iv administration.
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Animal Model:Nude (male and female, 18-20 g, xenograft model of human hepatic cancer SMMC-7721 cells)[1]
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Dosage:15 mg/kg
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Administration:i.v.; single dose; samples harvested at 0.25, 1, 2, 4, 8 h
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Result:Simmitecan and its active metabolite L-2-Z rapidly distributed to tissues, reaching peak concentrations 15 minutes after dosing.
Chemical Information
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CAS No. 951290-31-6
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Molecular Weight 598.70
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Formula C34H38N4O6
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SMILES
O=C1N2C(C=3C(C2)=CC=4C(N3)=CC=C(OC(=O)N5CCC(CC5)N6CCCCC6)C4CC=C)=CC7=C1COC(=O)[C@@]7(CC)O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Hu ZY, et al. Pharmacokinetic evaluation of the anticancer prodrug simmitecan in different experimental animals. Acta pharmacologica Sinica. 2013 Nov;34(11):1437-48. [Content Brief]
[2]. Zhou J, et al. A validated HPLC-MS/MS method for determination of simmitecan and its metabolite chimmitecan in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor. Journal of separation science. 2021 Nov;44(21):3959-3966. [Content Brief]
[3]. Zhang Q, et al. A Phase Ib Study of the Simmitecan Single Agent and in Combination With 5-Fluorouracil/Leucovorin or Thalidomide in Patients With Advanced Solid Tumor. Frontiers in pharmacology. 2022;13:833583. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Simmitecan Related Classifications
HY-107133A Related Classifications
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