Apaziquone
Apaziquone, also known as EO9, EOquin, is a n indolequinone bioreductive prodrug and analog of mitomycin C with potential antineoplastic and radiosensitization activities. Apaziquone is converted to active metabolites in hypoxic cells by intracellular reductases, which are present in greater amounts in hypoxic tumor cells. The active metabolites alkylate DNA, resulting in apoptotic cell death. This agent displays activity towards both hypoxic solid tumors, which exhibits higher expression of cytochrome P450 reductase, and well-oxygenated malignant cells that overexpress the bioreductive enzyme NQO1 (NAD(P)H
1: Phillips RM, Hendriks HR, Peters GJ; EORTC-Pharmacology and Molecular Mechanism Group. EO9 (Apaziquone): from the clinic to the laboratory and back again. Br J Pharmacol. 2013 Jan;168(1):11-8. doi: 10.1111/j.1476-5381.2012.01996.x. Review. PubMed PMID: 22509926; PubMed Central PMCID: PMC3569998.
2: Hendricksen K, Cornel EB, de Reijke TM, Arentsen HC, Chawla S, Witjes JA. Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer. J Urol. 2012 Apr;187(4):1195-9. doi: 10.1016/j.juro.2011.11.101. Epub 2012 Feb 14. PubMed PMID: 22335860.
3: Yutkin V, Chin J. Apaziquone as an intravesical therapeutic agent for urothelial non-muscle-invasive bladder cancer. Expert Opin Investig Drugs. 2012 Feb;21(2):251-60. doi: 10.1517/13543784.2012.646081. Epub 2011 Dec 21. Review. PubMed PMID: 22188461.
4: Arentsen HC, Hendricksen K, Hulsbergen-van de Kaa CA, Reddy G, Oosterwijk E, Alfred Witjes J. The orthotopic Fischer/AY-27 rat bladder urothelial cell carcinoma model to test the efficacy of different apaziquone formulations. Urol Oncol. 2012 Jan-Feb;30(1):64-8. doi: 10.1016/j.urolonc.2009.10.002. Epub 2009 Nov 27. PubMed PMID: 19945311.
5: Jain A, Phillips RM, Scally AJ, Lenaz G, Beer M, Puri R. Response of multiple recurrent TaT1 bladder cancer to intravesical apaziquone (EO9): comparative analysis of tumor recurrence rates. Urology. 2009 May;73(5):1083-6. doi: 10.1016/j.urology.2007.12.062. Epub 2009 Feb 20. PubMed PMID: 19232688.
6: Hendricksen K, van der Heijden AG, Cornel EB, Vergunst H, de Reijke TM, van Boven E, Smits GA, Puri R, Gruijs S, Witjes JA. Two-year follow-up of the phase II marker lesion study of intravesical apaziquone for patients with non-muscle invasive bladder cancer. World J Urol. 2009 Jun;27(3):337-42. doi: 10.1007/s00345-009-0382-4. Epub 2009 Feb 13. PubMed PMID: 19214526; PubMed Central PMCID: PMC2694322.
7: Witjes JA, Kolli PS. Apaziquone for non-muscle invasive bladder cancer: a critical review. Expert Opin Investig Drugs. 2008 Jul;17(7):1085-96. doi: 10.1517/13543784.17.7.1085 . Review. PubMed PMID: 18549344.
8: Hendricksen K, Gleason D, Young JM, Saltzstein D, Gershman A, Lerner S, Witjes JA. Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer. J Urol. 2008 Jul;180(1):116-20. doi: 10.1016/j.juro.2008.03.031. Epub 2008 May 15. PubMed PMID: 18485407.
9: Vainchtein LD, Rosing H, Mirejovsky D, Huynh V, Lenaz L, Schellens JH, Beijnen JH. Enhanced resolution triple-quadrupole mass spectrometry for ultra-sensitive and quantitative analysis of the investigational anticancer agent EO9 (apaziquone) and its metabolite EO5a in human and dog plasma to support (pre)-clinical studies of EOquin given intravesically. Rapid Commun Mass Spectrom. 2008;22(4):462-70. doi: 10.1002/rcm.3387. PubMed PMID: 18231986.
10: Vainchtein LD, Rosing H, Mirejovsky D, Huynh V, Lenaz L, Hillebrand MJ, Schellens JH, Beijnen JH. Quantitative analysis of EO9 (apaziquone) and its metabolite EO5a in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray tandem mass spectrometry. J Mass Spectrom. 2006 Oct;41(10):1268-76. PubMed PMID: 16981212.
2: Hendricksen K, Cornel EB, de Reijke TM, Arentsen HC, Chawla S, Witjes JA. Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer. J Urol. 2012 Apr;187(4):1195-9. doi: 10.1016/j.juro.2011.11.101. Epub 2012 Feb 14. PubMed PMID: 22335860.
3: Yutkin V, Chin J. Apaziquone as an intravesical therapeutic agent for urothelial non-muscle-invasive bladder cancer. Expert Opin Investig Drugs. 2012 Feb;21(2):251-60. doi: 10.1517/13543784.2012.646081. Epub 2011 Dec 21. Review. PubMed PMID: 22188461.
4: Arentsen HC, Hendricksen K, Hulsbergen-van de Kaa CA, Reddy G, Oosterwijk E, Alfred Witjes J. The orthotopic Fischer/AY-27 rat bladder urothelial cell carcinoma model to test the efficacy of different apaziquone formulations. Urol Oncol. 2012 Jan-Feb;30(1):64-8. doi: 10.1016/j.urolonc.2009.10.002. Epub 2009 Nov 27. PubMed PMID: 19945311.
5: Jain A, Phillips RM, Scally AJ, Lenaz G, Beer M, Puri R. Response of multiple recurrent TaT1 bladder cancer to intravesical apaziquone (EO9): comparative analysis of tumor recurrence rates. Urology. 2009 May;73(5):1083-6. doi: 10.1016/j.urology.2007.12.062. Epub 2009 Feb 20. PubMed PMID: 19232688.
6: Hendricksen K, van der Heijden AG, Cornel EB, Vergunst H, de Reijke TM, van Boven E, Smits GA, Puri R, Gruijs S, Witjes JA. Two-year follow-up of the phase II marker lesion study of intravesical apaziquone for patients with non-muscle invasive bladder cancer. World J Urol. 2009 Jun;27(3):337-42. doi: 10.1007/s00345-009-0382-4. Epub 2009 Feb 13. PubMed PMID: 19214526; PubMed Central PMCID: PMC2694322.
7: Witjes JA, Kolli PS. Apaziquone for non-muscle invasive bladder cancer: a critical review. Expert Opin Investig Drugs. 2008 Jul;17(7):1085-96. doi: 10.1517/13543784.17.7.1085 . Review. PubMed PMID: 18549344.
8: Hendricksen K, Gleason D, Young JM, Saltzstein D, Gershman A, Lerner S, Witjes JA. Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer. J Urol. 2008 Jul;180(1):116-20. doi: 10.1016/j.juro.2008.03.031. Epub 2008 May 15. PubMed PMID: 18485407.
9: Vainchtein LD, Rosing H, Mirejovsky D, Huynh V, Lenaz L, Schellens JH, Beijnen JH. Enhanced resolution triple-quadrupole mass spectrometry for ultra-sensitive and quantitative analysis of the investigational anticancer agent EO9 (apaziquone) and its metabolite EO5a in human and dog plasma to support (pre)-clinical studies of EOquin given intravesically. Rapid Commun Mass Spectrom. 2008;22(4):462-70. doi: 10.1002/rcm.3387. PubMed PMID: 18231986.
10: Vainchtein LD, Rosing H, Mirejovsky D, Huynh V, Lenaz L, Hillebrand MJ, Schellens JH, Beijnen JH. Quantitative analysis of EO9 (apaziquone) and its metabolite EO5a in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray tandem mass spectrometry. J Mass Spectrom. 2006 Oct;41(10):1268-76. PubMed PMID: 16981212.
| Chemical | |
|---|---|
| CAS Num | 114560-48-4 |
| Chemical Formula | C15H16N2O4 |
| Molecular Weight | 288.3 |
| IUPAC Chemical Name | 5-(aziridin-1-yl)-3-(hydroxymethyl)-2-[(E)-3-hydroxyprop-1-enyl]-1-methylindole-4,7-dione |
| Exact Mass | 288.11101 |
| Elemental Analysis | C, 62.49; H, 5.59; N, 9.72; O, 22.2 |
| Synonym | EO9; NSC 382459; EOquin; aziridinylquinone; Apaziquonum; Neoquin; Eoquin; NOR701. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C(C(N1CC1)=C2)C3=C(N(C)C(/C=C/CO)=C3CO)C2=O |
| Biological | |
| Targets and Effects | NA |
| Pathways | alkylating agent |
| Physical | |
| 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). |
| Shelf Life | >2 years if stored properly |
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