Piroxantrone

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205784

CAS#: 91441-23-5

Description: Piroxantrone, also known as CI942; PD111815, is a n anthrapyrazole antineoplastic antibiotic. Piroxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Although less cardiotoxic than doxorubicin, this agent exhibits a narrow spectrum of antineoplastic activity.


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Piroxantrone is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 205784
Name: Piroxantrone
CAS#: 91441-23-5
Chemical Formula: C21H25N5O4
Exact Mass: 411.19065
Molecular Weight: 411.4543
Elemental Analysis: C, 61.30; H, 6.12; N, 17.02; O, 15.55


Synonym: CI942; PD111815; CI 942; PD 111815; CI-942; PD-111815;Piroxantrone; oxanthrazole; oxantrazole; Piroxantrone HCl.

IUPAC/Chemical Name: 5-((3-aminopropyl)amino)-7,10-dihydroxy-2-(2-((2-hydroxyethyl)amino)ethyl)dibenzo[cd,g]indazol-6(2H)-one

SMILES Code: O=C1C2=C3C(N(CCNCCO)N=C3C4=C(O)C=CC(O)=C14)=CC=C2NCCCN


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Phase II study of Piroantrone reported in 1997: Piroxantrone was administered at a starting dose of 160 mg m2 given as a 1-h infusion every 3 weeks to 19 patients with histologically confirmed advanced, persistent, or recurrent squamous cell carcinoma of the cervix. All patients were required to have measurable disease and no prior chemotherapy. Eighteen women were evaluable for toxicity and response. Toxicity was modest and consisted primarily of myelosuppression with six (33%) patients experiencing grade 3 or 4 leukopenia. There were no complete (CR) or partial responses (PR) among the 18 evaluable patients. Six (33%) patients had stable disease while on treatment and 12 (67%) patients experienced progressive disease. Piroxantrone appears to have no beneficial effect in advanced or recurrent squamous cell cancer of the cervix at this dose and schedule.  (source: Am J Clin Oncol. 1997 Feb;20(1):84-5.).
 
Phase II study of Piroantrone reported in 1996: A phase II trial of the new anthrapyrazole piroxantrone was carried out by the Southwest Oncology Group in patients with advanced metastatic or recurrent endometrial cancer. A two-stage statistical design targeted accrual of 20 eligible patients. The starting dose of piroxantrone was 150 mg/m2 in patients without prior radiation therapy (RT) and 120 mg/m2 in patients with prior RT. There were 15 eligible patients, six of whom had received prior hormonal therapy while nine patients had not received prior hormonal therapy. Eight patients had received prior RT while seven patients had not received any prior RT. One to seven cycles of piroxantrone were administered. Dose escalation was feasible in four patients. No grade 5 toxicity was experienced by any patients. Most of the grade 4 (granulocytopenia in one) and grade 3 (leukopenia in three, granulocytopenia in three, anemia in two and thrombocytopenia in one) toxicity was related to myelosuppression. Grade 3 non-hematologic toxicities were nausea, fatigue and SGOT elevation. There was one partial response for a response rate of 7% (95% CI 0.2-32%) and median survival was 11 months (95% CI 3-13 months). The study was prematurely terminated due to lack of patient accrual. (source: Anticancer Drugs. 1996 Jul;7(5):527-30.)
 
 
 


References

1: Liang H, Wu X, Guziec LJ, Guziec FS Jr, Larson KK, Lang J, Yalowich JC, Hasinoff BB. A structure-based 3D-QSAR study of anthrapyrazole analogues of the anticancer agents losoxantrone and piroxantrone. J Chem Inf Model. 2006 Jul-Aug;46(4):1827-35. PubMed PMID: 16859314.

2: Hasinoff BB, Tran KT. The displacement of iron(III) from its complexes with the anticancer drugs piroxantrone and losoxantrone by the hydrolyzed form of the cardioprotective agent dexrazoxane. J Inorg Biochem. 1999 Nov-Dec;77(3-4):257-9. PubMed PMID: 10643663.

3: Herman EH, Zhang J, Hasinoff BB, Tran KT, Chadwick DP, Clark JR Jr, Ferrans VJ. Comparison of the chronic toxicity of piroxantrone, losoxantrone and doxorubicin in spontaneously hypertensive rats. Toxicology. 1998 Jun 26;128(1):35-52. PubMed PMID: 9704904.

4: Lincoln S, Blessing JA, McGehee R, Lentz SS. Phase II trial of piroxantrone in advanced squamous cell carcinoma of the cervix: a Gynecological Oncology Group study. Am J Clin Oncol. 1997 Feb;20(1):84-5. PubMed PMID: 9020296.

5: Malviya VK, Liu PY, Goldberg DA, Hantel A, O'Toole RV, Roach RW, Conrad ME, Alberts DS. A phase II trial of piroxantrone in endometrial cancer: Southwest Oncology Group study 8918. Anticancer Drugs. 1996 Jul;7(5):527-30. PubMed PMID: 8862719.

6: Albain KS, Liu PY, Hantel A, Poplin EA, O'Toole RV, Wade JL 3rd, Maddox AM, Alberts DS. A phase II trial of piroxantrone in advanced ovarian carcinoma after failure of platinum-based chemotherapy: Southwest Oncology Group Study 8904. Gynecol Oncol. 1995 Jun;57(3):407-11. PubMed PMID: 7774846.

7: Sosman JA, Flaherty LE, Liu PY, Fletcher W, Thompson JA, Hantel A, Sondak V. A phase II trial of piroxantrone in disseminated malignant melanoma. A Southwest Oncology Group study. Invest New Drugs. 1995;13(1):83-7. PubMed PMID: 7499114.

8: Ingle JN, Kuross SA, Mailliard JA, Loprinzi CL, Jung SH, Nelimark RA, Krook JE, Long HJ. Evaluation of piroxantrone in women with metastatic breast cancer and failure on nonanthracycline chemotherapy. Cancer. 1994 Sep 15;74(6):1733-8. PubMed PMID: 8082075.

9: Pazdur R, Bready B, Scalzo AJ, Brandof JE, Close DR, Kolbye S, Winn RJ. Phase II trial of piroxantrone in metastatic gastric adenocarcinoma. Invest New Drugs. 1994;12(3):263-5. PubMed PMID: 7896547.

10: Hantel A, Tangen C, Gluck WL, Macdonald JS. Phase II trial of piroxantrone in gastric carcinoma. A Southwest Oncology Group study. Invest New Drugs. 1994;12(2):159-61. PubMed PMID: 7860236.

11: Ravdin PM, Green S, Doroshow JH, Martino S. Phase II trial of piroxantrone in metastatic breast cancer. A Southwest Oncology Group study. Invest New Drugs. 1994;12(4):333-6. PubMed PMID: 7775136.

12: Zalupski MM, Benedetti J, Balcerzak SP, Hutchins LF, Belt RJ, Hantel A, Goodwin JW. Phase II trial of piroxantrone for advanced or metastatic soft tissue sarcomas. A Southwest Oncology Group study. Invest New Drugs. 1993 Nov;11(4):337-41. PubMed PMID: 8157477.

13: Jenkins TR, Tangen C, Macdonald JS, Weiss G, Chapman R, Hantel A. A phase II trial of piroxantrone in adenocarcinoma of the pancreas. A Southwest Oncology Group study. Invest New Drugs. 1993 Nov;11(4):329-31. PubMed PMID: 8157474.

14: Berg SL, Balis FM, Godwin KS, Poplack DG. Pharmacokinetics, cerebrospinal fluid penetration, and metabolism of piroxantrone in the rhesus monkey. Invest New Drugs. 1993 Nov;11(4):255-61. PubMed PMID: 8157468.

15: Savarese DM, Denicoff AM, Berg SL, Hillig M, Baker SP, O'Shaughnessy JA, Chow C, Otterson GA, Balis FM, Poplack DG, et al. Phase I study of high-dose piroxantrone with granulocyte colony-stimulating factor. J Clin Oncol. 1993 Sep;11(9):1795-803. PubMed PMID: 7689093.

16: Berg SL, Savarese DM, Balis FM, Denicoff AM, Hillig M, O'Shaughnessy JA, Poplack DG, Cowan KH. Pharmacokinetics of piroxantrone in a phase I trial of piroxantrone and granulocyte-colony stimulating factor. Cancer Res. 1993 Jun 1;53(11):2587-90. PubMed PMID: 7684320.

17: Taylor SA, Benedetti J, Schuller D, Richman SP, Broun GO, Hantel A. Phase II trial of piroxantrone in patients with recurrent and metastatic squamous cell carcinoma of the head and neck. A Southwest Oncology Group trial. Invest New Drugs. 1993 May-Aug;11(2-3):227-9. PubMed PMID: 8262737.

18: Chang AY, Kim K, Glick J, Anderson T, Karp D, Johnson D. Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results. J Natl Cancer Inst. 1993 Mar 3;85(5):388-94. PubMed PMID: 8094467.

19: Allen A, Wolf M, Crawford ED, Davis MP, Natale RB, Barnett ML. Phase II evaluation of piroxantrone in renal cell carcinoma. A Southwest Oncology Group Study. Invest New Drugs. 1992 Jul;10(2):129-32. PubMed PMID: 1500267.

20: Williamson SK, Crowley JJ, Livingston R, Hantel A, Doroshow JH. Phase II trial of piroxantrone in advanced non-small cell carcinoma of the lung. A Southwest Oncology Group study. Invest New Drugs. 1992 Apr;10(1):29-30. PubMed PMID: 1318871.

21: Hantel A, Donehower RC, Rowinsky EK, Vance E, Clarke BV, McGuire WP, Ettinger DS, Noe DA, Grochow LB. Phase I study and pharmacodynamics of piroxantrone (NSC 349174), a new anthrapyrazole. Cancer Res. 1990 Jun 1;50(11):3284-8. PubMed PMID: 2334921.

22: Clarke BV, Harwood KV, Donehower R. Local toxicity of piroxantrone: an anthrapyrazole with irritant and vesicant properties similar to those of doxorubicin. J Natl Cancer Inst. 1989 Sep 6;81(17):1331-2. PubMed PMID: 2769786.

23: Frank SK, Mathiesen DA, Szurszewski M, Kuffel MJ, Ames MM. Preclinical pharmacology of the anthrapyrazole analog oxantrazole (NSC-349174, piroxantrone). Cancer Chemother Pharmacol. 1989;23(4):213-8. PubMed PMID: 2924379.