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Pirarubicin hydrochloride (THP), an analogue of anthracycline, is an anti-neoplastic doxorubicin which acts as a topoisomerase II inhibitor, and is used for treatment of various cancers, in particular, solid tumors. It inhibits DNA replication by intercalating into DNA, interacting with Topo II (topoisomerase II). M5076 cells quickly absorb pirarubicin, and its intracellular concentration surpasses that of doxorubicin by a factor of 2.5. When it comes to the 50% concentration in vitro that inhibits cell growth, pirarubicin works better than doxorubicin. In MG-63 cells, pirarubicin increases Bax expression while suppressing the expression of PCNA, cyclin D1, cyclin E, and Bcl-2.
Physicochemical Properties
| Molecular Formula | C32H38CLNO12 |
| Molecular Weight | 664.09663 |
| Exact Mass | 663.208 |
| Elemental Analysis | C, 57.88; H, 5.77; Cl, 5.34; N, 2.11; O, 28.91 |
| CAS # | 95343-20-7 |
| Related CAS # | Pirarubicin;72496-41-4 |
| PubChem CID | 20846247 |
| Appearance | Pink to red solid powder |
| Boiling Point | 834.7ºC at 760mmHg |
| Flash Point | 458.6ºC |
| LogP | 3.054 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 13 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 46 |
| Complexity | 1120 |
| Defined Atom Stereocenter Count | 7 |
| 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 |
| InChi Key | ZPHYPKKFSHAVOE-YZIXBPQXSA-N |
| 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 |
| 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 |
| 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 |
| 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 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) |
Biological Activity
| Targets | Topoisomerase II | |
| ln Vitro |
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| ln Vivo |
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| 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]. | |
| 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]. | |
| 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]. | |
| References |
[1]. Cytotoxic effect of topoisomerase II inhibitors against adriamycin- and etoposide-resistant small cell lung cancer sublines. Gan To Kagaku Ryoho. 1993 May;20(7):929-35. [2]. Relationships between the in vitro cytotoxicity and transport characteristics of pirarubicin and doxorubicin in M5076 ovarian sarcoma cells, and comparison with those in Ehrlich ascites carcinoma cells. Cancer Chemother Pharmacol. 2002 Mar;49(3):244-50. Epub 2002 Jan 8. [3]. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells. Biochem Biophys Res Commun. 2015 May 1;460(2):380-5. [4]. Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity. J Asian Nat Prod Res. 2017 Oct 27:1-13. |
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| Additional Infomation |
Pirarubicin Hydrochloride is the hydrochloride salt form of pirarubicin, an analogue of the anthracycline antineoplastic antibiotic doxorubicin with antineoplastic activity. Pirarubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. This agent is less cardiotoxic than doxorubicin and exhibits activity against some doxorubicin-resistant cell lines. See also: Pirarubicin (annotation moved to). |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~20.8 mg/mL (~31.4 mM) H2O: < 0.1 mg/mL |
| 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 |