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| Targets |
Topoisomerase II
Pirarubicin targets topoisomerase II, an enzyme that is essential for DNA replication and cell division. By inhibiting topoisomerase II, Pirarubicin prevents the religation of DNA double-strand breaks, leading to DNA damage and cell death. It is an anthracycline antibiotic that intercalates into DNA and generates reactive oxygen species, contributing to its antitumor activity. |
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| ln Vitro |
Pirarubicin is quickly absorbed by M5076 cells, and is more than 2.5 times as concentrated intracellularly as doxorubicin. The 50% cell growth-inhibitory concentration in vitro is better achieved by pirarubicin than by doxorubicin. G0/G1 cell cycle arrest in MG-63 cells is brought on by pirarubicin. In MG-63 cells, parorubicin increases the expression of Bax while suppressing the expression of Bcl-2, PCNA, cyclin D1, and cyclin E. In the aorta with endothelium, pirarubicin significantly relaxes contractions brought on by noradrenaline (0.1 μM), but not in the aorta without endothelium. Methylene blue (5 μM), hydroquinone (100 μM), phenidone (50 μM), hemoglobin (1 μM), and p-bromophenacyl bromide (50 μM) all inhibit pirarubicin-induced relaxation, but indomethacin (25 μM) does not. Between two and five times as potent as Adriamycin in SKUT1B, HEC1A, and BG1 cell lines is pyrarubicin. The G2 block dose-response pattern of pirarubicin is also reversed, meaning that at high doses, the cell cycle kinetics would resemble those of untreated controls.
In vitro, Pirarubicin Hydrochloride acts as a topoisomerase II inhibitor. It demonstrates potent antitumor activity against various cancer cell lines. As an anthracycline antibiotic, it intercalates into DNA and inhibits DNA replication. The compound's activity is typically assessed by measuring cell viability, DNA damage markers, and topoisomerase II inhibition in cancer cell lines. |
| ln Vivo |
Pirarubicin decreases the tumor weight in M5076 solid tumor-bearing mice to 60% of the control level, while doxorubicin has no effect. When injected via the hepatic intra-arterial (h.i.a.) route, both pirarubicin and epirubicin are effective against V x 2 tumors; however, pirarubicin exhibits stronger activity than epirubicin.
In vivo, Pirarubicin Hydrochloride is used clinically for the treatment of various cancers, particularly solid tumors. It is administered via intravenous injection. The compound's improved pharmacokinetic profile and reduced cardiotoxicity compared to doxorubicin make it a valuable therapeutic option. Its efficacy has been demonstrated in clinical studies for breast cancer, gastric cancer, and other malignancies. |
| Enzyme Assay |
Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients[3].
In vitro enzyme inhibition assays for Pirarubicin Hydrochloride are performed using purified topoisomerase II enzyme. The enzyme is incubated with DNA substrate and ATP in the presence of increasing concentrations of the compound. The extent of DNA relaxation or cleavage is measured by gel electrophoresis, and the IC₅₀ is calculated from the inhibition curve. |
| Cell Assay |
Cell survival analysis is done using MTS. In short, 96-well plates are used to plate cells in triplicate, with 2 × 103 cells per well, and the cells are then cultured in growth medium. Following that, cells are exposed to pirarubicin for 24 hours at three different concentrations: 2.5 μg/mL, 5 μg/mL, and 10 μg/mL. Once added, the MTS reagent (5 mg/mL) is incubated for 4 hours at 37°C. A microplate reader is used to measure the absorbance at 490 nm[3].
In vitro cellular assays for Pirarubicin Hydrochloride are performed using cancer cell lines such as breast, gastric, or leukemia cells. Cells are treated with the compound at various concentrations for 48-72 hours, and cell viability is assessed using MTT, CCK-8, or SRB assays. DNA damage is evaluated by measuring γ-H2AX foci or comet assays. Apoptosis is assessed by flow cytometry using annexin V staining. |
| Animal Protocol |
A single injection into the caudal vein of 18 mg/kg pirarubicin creates an acute cardiac toxicity model. Thirty-six rats are randomized equally into six groups: low-dose rutin (25 mg/kg), middle-dose rutin (50 mg/kg), high-dose rutin (100 mg/kg), cardiac injury (THP) model, and dexrazoxane (180 mg/kg). The rats in the rutin-treated group receive a single injection of 18 mg/kg of pirarubicin via the caudal vein, as well as varying doses of rutin and CMC-Na by gavage for seven days. For six days, rats in the dexrazoxane-treated group are gavaged with sodium carboxymethylcellulose (CMC-Na). On day 7, rats receive an intraperitoneal injection of 40 mg/kg dexrazoxane and a caudal vein injection of 18 mg/kg pirarubicin. Rats in the THP model group are given CMC-Na by gavage for seven days, and on day seven, they are given an injection of pirarubicin (18 mg/kg) into the caudal vein. The normal control group of rats is given CMC-Na by gavage for seven days, and on day seven, they receive an injection of saline into their caudal vein[4].
In vivo animal experiments for Pirarubicin Hydrochloride are conducted in mouse xenograft models bearing human tumor cells. The compound is administered via intravenous injection at various doses (typically mg/kg range). Tumor volume is measured periodically to assess anti-tumor efficacy, and body weight is monitored to evaluate toxicity. Cardiotoxicity is assessed by measuring cardiac function markers. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Pirarubicin Hydrochloride have been characterized in preclinical and clinical studies. The compound has a molecular weight of 664.10 and molecular formula C₃₂H₃₈ClNO₁₂. It is soluble in DMSO (10 mM). It should be stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years. It is administered via intravenous injection.
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| Toxicity/Toxicokinetics |
Pirarubicin Hydrochloride is an anthracycline antibiotic with well-characterized toxicity. Its cardiotoxicity profile is improved compared to doxorubicin. Common adverse effects include myelosuppression, nausea, vomiting, and alopecia. The compound is for research use only and is not approved for clinical use in all jurisdictions. Standard laboratory safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
Pirarubicin hydrochloride is the hydrochloride form of pirarubicin, an analogue of the anthracycline antitumor antibiotic doxorubicin, possessing antitumor activity. Pirarubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair, as well as RNA and protein synthesis. This drug has lower cardiotoxicity than doxorubicin and is also effective against some doxorubicin-resistant cell lines.
See also: Pirarubicin (note moved to). Pirarubicin Hydrochloride (THP Hydrochloride) is an anthracycline antibiotic and topoisomerase II inhibitor with CAS number 95343-20-7, molecular formula C₃₂H₃₈ClNO₁₂, and molecular weight 664.10. It is a doxorubicin analogue used for the treatment of solid tumors. The compound offers improved pharmacokinetics and reduced cardiotoxicity. This product is for research use only. |
| Molecular Formula |
C32H38CLNO12
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|---|---|
| Molecular Weight |
664.09663
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| Exact Mass |
663.208
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| Elemental Analysis |
C, 57.88; H, 5.77; Cl, 5.34; N, 2.11; O, 28.91
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| CAS # |
95343-20-7
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| Related CAS # |
Pirarubicin;72496-41-4
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| PubChem CID |
20846247
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| Appearance |
Pink to red solid powder
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| Boiling Point |
834.7ºC at 760mmHg
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| Flash Point |
458.6ºC
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| LogP |
3.054
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
46
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| Complexity |
1120
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| Defined Atom Stereocenter Count |
7
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| SMILES |
O([C@@H]1O[C@@H](C)[C@@H](O[C@H]2OCCCC2)[C@@H](N)C1)[C@H]1C[C@](O)(C(=O)CO)CC2=C(C3C(=O)C4C=CC=C(C=4C(=O)C=3C(=C12)O)OC)O.Cl
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| InChi Key |
ZPHYPKKFSHAVOE-YZIXBPQXSA-N
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| InChi Code |
InChI=1S/C32H37NO12.ClH/c1-14-31(45-21-8-3-4-9-42-21)17(33)10-22(43-14)44-19-12-32(40,20(35)13-34)11-16-24(19)30(39)26-25(28(16)37)27(36)15-6-5-7-18(41-2)23(15)29(26)38;/h5-7,14,17,19,21-22,31,34,37,39-40H,3-4,8-13,33H2,1-2H3;1H/t14-,17-,19-,21+,22-,31+,32-;/m0./s1
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| Chemical Name |
(7S,9S)-7-[(2R,4S,5S,6S)-4-amino-6-methyl-5-[(2R)-oxan-2-yl]oxyoxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride
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| Synonyms |
Pirarubicin HCl; Pirarubicin hydrochloride; Pirarubicin (Hydrochloride); Theprubicin; THP hydrochloride; E7V83174BE; 5,12-Naphthacenedione,10-[[3-amino-2,3,6-trideoxy-4-O-[(2R)-tetrahydro-2H-pyran-2-yl]-a-L-lyxo-hexopyranosyl]oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S,10S)-; Pirarubicin hydrochloride
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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: ~20.8 mg/mL (~31.4 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5058 mL | 7.5290 mL | 15.0580 mL | |
| 5 mM | 0.3012 mL | 1.5058 mL | 3.0116 mL | |
| 10 mM | 0.1506 mL | 0.7529 mL | 1.5058 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04437160 | Recruiting | Drug: Epirubicin or Pirarubicin Drug: Cyclophosphamide |
Triple Negative Breast Cancer | Chinese Academy of Medical Sciences |
February 1, 2020 | Phase 2 |
| NCT05287308 | Not yet recruiting | Drug: pirarubicin Drug: cyclophosphamide |
Breast Cancer | Chinese Academy of Medical Sciences |
March 2022 | Not Applicable |
| NCT02613026 | Completed | Drug: Pirarubicin Drug: Docetaxel |
Breast Neoplasms | 307 Hospital of PLA | July 2009 | Phase 3 |
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