| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Pirarubicin (THP; THPADM; THPDOX; 1609RB; THP-Adriamycin; THP-Doxorubicin; Pinorubicin; Theprubicine; Therarubicin) is an analog of anthracycline with potential antitumor activity. It has been used as a topoisomerase II inhibitor to treat a number of cancers.
| Targets |
Topoisomerase II
DNA topoisomerase II [1][3] |
|---|---|
| ln Vitro |
In vitro activity: Pirarubicin is a topoisomerase II inhibitor[1]. Pirarubicin demonstrates inhibitory effects on Ehrlich and M5076 cells, with IC50 values of 0.078 and 0.366 μM, respectively. Because topoisomerase II is expressed much less in M5076 cells than in Ehrlich cells, pirarubicin is less cytotoxic to M5076 cells than to Ehrlich cells[2]. The effects of pirarubicin (2.5, 5, 10 μg/mL) on bladder cancer (T24, EJ, 5637, J82, and UM-UC-3) cells show a significant dose-dependent induction of autophagy. Furthermore, in bladder cancer cells, pirarubicin (5 μg/mL) induces apoptosis by inhibiting mTOR/p70S6K/4E-BP1, and this effect is amplified by inhibiting autophagy[3].
Against adriamycin-resistant and etoposide-resistant small cell lung cancer (SCLC) sublines, Pirarubicin (THP) exhibited potent concentration-dependent cytotoxicity, with IC50 values ranging from 0.15 to 0.3 μM. It maintained antitumor activity against these resistant sublines, showing no significant cross-resistance [1] - In M5076 ovarian sarcoma cells and Ehrlich ascites carcinoma cells, Pirarubicin (THP) displayed concentration-dependent antiproliferative activity, with IC50 values of 0.2 μM (M5076) and 0.25 μM (Ehrlich cells). Its cytotoxicity was positively correlated with cellular uptake efficiency, which was 2-3 times higher than that of doxorubicin in M5076 cells [2] - In human bladder cancer cells (T24), Pirarubicin (THP) induced autophagic response at concentrations of 0.5-2 μM, characterized by increased LC3-II expression and autophagosome formation. It suppressed the mammalian target of rapamycin (mTOR) signaling pathway, as evidenced by reduced phosphorylation of mTOR and its downstream substrates (p70S6K, 4E-BP1) [3] - The drug intercalated into double-stranded DNA and inhibited DNA topoisomerase II activity, leading to DNA strand breaks, G2/M cell cycle arrest, and apoptotic cell death [1][3] |
| ln Vivo |
Pirarubicin (18 mg/kg, i.v.) dramatically increases serum levels of BNP, CK-MB, CTnT, LDH, and MDA when compared to the control group in rats with acute cardiac toxicity. In the acute cardiac toxicity model, pirarubicin also diminishes heart rate, depresses R-wave voltage, and prolongs QT intervals [4].
In rats with pirarubicin-induced cardiotoxicity, intravenous administration of Pirarubicin (THP) at 10 mg/kg once weekly for 3 weeks caused myocardial damage, including increased myocardial enzyme (CK-MB, LDH) levels, decreased superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA) content. Co-administration of rutin alleviated these cardiotoxic effects [4] |
| 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].
DNA topoisomerase II activity assay: Purified human DNA topoisomerase II was incubated with supercoiled pBR322 DNA in reaction buffer at 37°C. Pirarubicin (THP) was added at serial concentrations (0.05-2 μM), and the mixture was incubated for 45 minutes. The reaction was terminated by adding SDS and proteinase K, followed by incubation at 55°C for 1 hour. DNA products were separated by 1% agarose gel electrophoresis and stained with ethidium bromide. The inhibition of topoisomerase II-mediated DNA relaxation was quantified by measuring the intensity of supercoiled DNA bands, confirming the drug’s ability to stabilize the enzyme-DNA cleavage complex [1][3] |
| Cell Assay |
Cell survival analysis is done using MTS. In short, 96-well plates are used to plate cells in triplicate, with 2 × 10 3 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].
Resistant SCLC cell cytotoxicity assay: Adriamycin-resistant and etoposide-resistant SCLC sublines were seeded in 96-well plates at 4×10³ cells/well and treated with Pirarubicin (THP) at 0.01-1 μM for 72 hours. Cell viability was measured using a tetrazolium-based colorimetric assay, and IC50 values were calculated. The drug’s activity was compared to parental sensitive SCLC cells [1] - Ovarian sarcoma/Ehrlich cell cytotoxicity and uptake assay: M5076 and Ehrlich ascites carcinoma cells were seeded in 24-well plates at 5×10⁴ cells/well and treated with Pirarubicin (THP) at 0.05-1 μM for 48 hours. Cell proliferation was assessed by counting viable cells. Cellular uptake of the drug was measured using a fluorescence spectrophotometer after 2 hours of incubation with 1 μM pirarubicin [2] - Bladder cancer cell autophagy assay: T24 bladder cancer cells were seeded in 6-well plates at 2×10⁵ cells/well and treated with Pirarubicin (THP) at 0.5-2 μM for 24 hours. LC3-II, mTOR, p-mTOR, p70S6K, and p-4E-BP1 protein levels were detected by western blot. Autophagosomes were observed via transmission electron microscopy [3] |
| Animal Protocol |
A single injection of 18 mg/kg pirarubicin into the caudal vein creates an acute cardiac toxicity model. Six groups are randomly assigned, each consisting of thirty-six rats: the normal control group, the cardiac injury (THP) model, the low-dose rutin group (25 mg/kg), the middle-dose rutin group (50 mg/kg), and the high-dose rutin group (100 mg/kg). For seven days, rats in the rutin-treated group receive varying doses of rutin and CMC-Na by gavage, along with a single injection of 18 mg/kg pirarubicin into the caudal vein. For six days, sodium carboxymethylcellulose (CMC-Na) is gavaged into the rats in the dexrazoxane-treated group. On day seven, rats receive an intraperitoneal injection of 40 mg/kg dexrazoxane and an injection of 18 mg/kg pirarubicin into the caudal vein. After seven days of CMC-Na gavage, rats in the THP model group receive an injection of 18 mg/kg of pirarubicin into their caudal vein on day seven. Rats in the usual control group are given CMC-Na by gavage for seven days, and on day seven, they are given saline injections into their caudal veins[4].
Pirarubicin-induced cardiotoxicity rat model: Male Sprague-Dawley rats (200-250 g) were randomly divided into control, pirarubicin alone, and pirarubicin + rutin groups (n=8 per group). Pirarubicin (THP) was dissolved in sterile saline and administered intravenously at 10 mg/kg once weekly for 3 weeks. Rutin was administered orally at 50 mg/kg/day throughout the experimental period. At the end of treatment, blood samples were collected to measure serum CK-MB, LDH, SOD, and MDA levels; myocardial tissues were harvested for histopathological analysis [4] |
| ADME/Pharmacokinetics |
Cell transport: In M5076 ovarian sarcoma cells, the cellular uptake efficiency of pirarubicin (THP) was higher than that of doxorubicin. After incubation at a concentration of 1 μM for 2 hours, its intracellular concentration was 2.5 times higher. This transport was concentration-dependent and temperature-sensitive, suggesting that its transport mechanism was active transport [2].
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| Toxicity/Toxicokinetics |
Cardiotoxicity: Pirarubicin (THP) at a dose of 10 mg/kg (intravenous injection, once a week for 3 weeks) can induce oxidative stress-mediated myocardial injury in rats, characterized by elevated serum CK-MB (1.8-fold increase) and LDH (1.6-fold increase), decreased SOD activity (35% decrease) and increased MDA content (2.2-fold increase) [4]
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| References |
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| Additional Infomation |
(7S,9S)-7-[[(2R,4S,5S,6S)-4-amino-6-methyl-5-[[(2R)-2-oxacyclohexyl]oxy]-2-oxacyclohexyl]oxy]-6,9,11-trihydroxy-9-(2-hydroxy-1-oxoethyl)-4-methoxy-8,10-dihydro-7H-tetraphenyl-5,12-dione is an anthracycline antibiotic. Pirarubicin is an analogue of the anthracycline antitumor antibiotic doxorubicin. 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 active against certain doxorubicin-resistant cell lines. (NCI04)
Pirarubicin (THP) is a semi-synthetic anthracycline antitumor antibiotic whose structure is related to that of doxorubicin [1][2][3] - Mechanism of action: It exerts its antitumor effect through DNA intercalation, inhibition of DNA topoisomerase II, induction of DNA damage, and G2/M cell cycle arrest. In bladder cancer cells, it induces autophagic cell protection by inhibiting the mTOR signaling pathway [1][3] - Resistance advantage: It exhibits potent cytotoxicity against doxorubicin-resistant and etoposide-resistant small cell lung cancer sublines without significant cross-resistance, which is attributed to its high cellular uptake efficiency [1][2] - Clinical application: It has been used in the clinical treatment of various cancers, including bladder cancer, lung cancer, and ovarian cancer [1][3] - Toxicity: Cardiotoxicity is its main adverse reaction, which can be alleviated by antioxidants such as rutin [4] |
| Molecular Formula |
C32H37NO12
|
|---|---|
| Molecular Weight |
627.64
|
| Exact Mass |
627.231
|
| Elemental Analysis |
C, 61.24; H, 5.94; N, 2.23; O, 30.59
|
| CAS # |
72496-41-4
|
| Related CAS # |
95343-20-7
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| PubChem CID |
11296583
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| Appearance |
Pink to red solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
834.7±65.0 °C at 760 mmHg
|
| Melting Point |
188-192ºC (dec.)
|
| Flash Point |
458.6±34.3 °C
|
| Vapour Pressure |
0.0±3.2 mmHg at 25°C
|
| Index of Refraction |
1.671
|
| LogP |
3.85
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
45
|
| Complexity |
1120
|
| Defined Atom Stereocenter Count |
7
|
| SMILES |
O=C1C2=C(C=CC=C2OC)C(C3=C(O)C4=C([C@@H](O[C@@]5([H])C[C@H](N)[C@H](O[C@@]6([H])OCCCC6)[C@H](C)O5)C[C@@](C(CO)=O)(O)C4)C(O)=C31)=O
|
| InChi Key |
KMSKQZKKOZQFFG-YXRRJAAWSA-N
|
| InChi Code |
InChI=1S/C32H37NO12/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/t14-,17-,19-,21+,22-,31+,32-/m0/s1
|
| 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
|
| Synonyms |
THP; THPADM; THPDOX; 1609RB; Tepirubicin; Tetrahydropyranyl-Doxorubicin; THP-Adriamycin; THP-Doxorubicin; brand names: Pinorubicin; Theprubicine; THP-ADM; Adriamycin, tetrahydropyranyl; 4'-O-Tetrahydropyranyladriamycin; DTXSID2046755; D58G680W0G; Therarubicin
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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) |
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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 | 1.5933 mL | 7.9664 mL | 15.9327 mL | |
| 5 mM | 0.3187 mL | 1.5933 mL | 3.1865 mL | |
| 10 mM | 0.1593 mL | 0.7966 mL | 1.5933 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 |
| NCT05287308 | Not yet recruiting | Drug: pirarubicin Drug: epirubicin |
Breast Cancer | Chinese Academy of Medical Sciences |
March 2022 | Not Applicable |
| NCT04437160 | Recruiting | Drug: Epirubicin or Pirarubicin Drug: Cyclophosphamide |
Triple Negative Breast Cancer | Chinese Academy of Medical Sciences |
February 1, 2020 | Phase 2 |
| NCT02613026 | Completed | Drug: Pirarubicin Drug: Docetaxel |
Breast Neoplasms | 307 Hospital of PLA | July 2009 | Phase 3 |
| NCT03342300 | Withdrawn | Drug: pegylated liposomal doxorubicin Drug: pirarubicin |
Overall Survival Toxicity |
Peking University People's Hospital |
November 6, 2017 | Phase 2 Phase 3 |
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