WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100910
Description: Valrubicin is a semisynthetic derivative of the antineoplastic anthracycline antibiotic doxorubicin. With a mechanism of action that appears to differ from doxorubicin, valrubicin is converted intracytoplasmically into N-trifluoroacetyladriamycin, which interacts with topoisomerase II, stabilizing the complex between the enzyme and DNA; consequently, DNA replication and repair and RNA and protein synthesis are inhibited and the cell cycle is arrested in the G2 phase. In addition, this agent accumulates in the cell cytoplasm where it inhibits protein kinase C (PKC). Valrubicin is less cardiotoxic than doxorubicin when administered systemically; applied topically, this agent shows excellent tissue penetration.
MedKoo Cat#: 100910
Chemical Formula: C34H36F3NO13
Exact Mass: 723.21387
Molecular Weight: 723.64
Elemental Analysis: C, 56.43; H, 5.01; F, 7.88; N, 1.94; O, 28.74
Synonym: Valrubicin, Valstar, Valtaxin, AD 32, AD32, AD-32
IUPAC/Chemical Name: 2-oxo-2-((2S,4S)-2,5,12-trihydroxy-4-(((2S,4S,5S,6S)-5-hydroxy-6-methyl-4-(2,2,2-trifluoroacetamido)tetrahydro-2H-pyran-2-yl)oxy)-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl)ethyl pentanoate
InChi Key: ZOCKGBMQLCSHFP-PIXAVGEUSA-N
InChi Code: InChI=1S/C34H36F3NO13/c1-4-5-9-21(40)49-13-20(39)33(47)11-16-24(19(12-33)51-22-10-17(27(41)14(2)50-22)38-32(46)34(35,36)37)31(45)26-25(29(16)43)28(42)15-7-6-8-18(48-3)23(15)30(26)44/h6-8,14,17,19,22,27,41,43,45,47H,4-5,9-13H2,1-3H3,(H,38,46)/t14-,17-,19-,22+,27+,33-/m0/s1
SMILES Code: CCCCC(OCC([C@@]1(O)C[C@H](O[C@@H]2C[C@H](NC(C(F)(F)F)=O)[C@H](O)[C@H](C)O2)C3=C(O)C4=C(C(C5=CC=CC(OC)=C5C4=O)=O)C(O)=C3C1)=O)=O
Valrubicin (N-trifluoroacetyladriamycin-14-valerate, trade name Valstar) is a chemotherapy drug used to treat bladder cancer. Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder. It was originally launched as Valstar in the U.S. in 1999 for intravesical therapy of Bacille Calmette-GuÃ©rin (BCG)-refractory carcinoma in situ of the urinary bladder in patients in whom cystectomy would be associated with unacceptable morbidity or mortality; however, it was voluntarily withdrawn in 2002 due to manufacturing issues.Valstar was relaunched on September 3, 2009. (The above information was directly from http://en.wikipedia.org/wiki/Valrubicin).
Valrubicin (N-trifluoroacetyladriamycin-14-valerate), a semisynthetic analog of the anthra-cycline doxorubicin, is a cytotoxic agent with the chemical name, (2S-cis)-2-[1,2,3,4, 6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-4-[[2,3,6-trideoxy-3-[(trifluoroacetyl)amino]-α-L-lyxo-hexopyranosyl]oxyl]-2-naphthacenyl]-2-oxoethyl pentanoate. Valrubicin is an orange or orange-red powder that is highly lipophilic, soluble in methylene chloride, ethanol, methanol and acetone, and relatively insoluble in water. Its chemical formula is C34H36F3NO13. VALSTARÂ® (valrubicin) Sterile Solution for Intravesical Instillation is intended for intra-vesical administration in the urinary bladder. It is supplied as a nonaqueous solution that should be diluted before intravesical administration. Each vial of VALSTAR contains valrubicin at a concentration of 40 mg/mL in 50% polyoxyl castor oil/50% dehydrated alcohol, USP without preservatives or other additives. The solution is sterile and nonpyro-genic.
Mechanism of Action:
Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II.
1: Laugesen IG, Hauge E, Andersen SM, Stenderup K, de Darko E, Dam TN, Rosada C. Valrubicin Activates PKCa in Keratinocytes: A Conceivable Mode of Action in Treating Hyper-Proliferative Skin Diseases. J Drugs Dermatol. 2013 Oct 1;12(10):1156-62. PubMed PMID: 24085052.
2: Dinney CP, Greenberg RE, Steinberg GD. Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-GuÃ©rin. Urol Oncol. 2012 May 9. [Epub ahead of print] PubMed PMID: 22575238.
3: Hauge E, Christiansen H, Rosada C, de DarkÃ³ E, Dam TN, Stenderup K. Topical valrubicin application reduces skin inflammation in murine models. Br J Dermatol. 2012 Aug;167(2):288-95. doi: 10.1111/j.1365-2133.2012.10964.x. Epub 2012 Jul 5. PubMed PMID: 22458650.
4: Sabnis N, Nair M, Israel M, McConathy WJ, Lacko AG. Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles. Int J Nanomedicine. 2012;7:975-83. doi: 10.2147/IJN.S28029. Epub 2012 Feb 22. PubMed PMID: 22393294; PubMed Central PMCID: PMC3289451.
5: Steinberg GD, Smith ND, Ryder K, Strangman NM, Slater SJ. Factors affecting valrubicin response in patients with bacillus Calmette-GuÃ©rin-refractory bladder carcinoma in situ. Postgrad Med. 2011 May;123(3):28-34. doi: 10.3810/pgm.2011.05.2281. PubMed PMID: 21566413.
6: Andersen SM, Rosada C, Dagnaes-Hansen F, Laugesen IG, de DarkÃ³ E, Dam TN, Stenderup K. Topical application of valrubicin has a beneficial effect on developing skin tumors. Carcinogenesis. 2010 Aug;31(8):1483-90. doi: 10.1093/carcin/bgq122. Epub 2010 Jun 16. PubMed PMID: 20554745.
7: Rosada C, Stenderup K, de DarkÃ³ E, Dagnaes-Hansen F, Kamp S, Dam TN. Valrubicin in a topical formulation treats psoriasis in a xenograft transplantation model. J Invest Dermatol. 2010 Feb;130(2):455-63. doi: 10.1038/jid.2009.277. Epub 2009 Sep 10. PubMed PMID: 19741712.
8: Wu S, Sun C, Pan Y. Preparative counter-current chromatography purification of valrubicin (AD-32) from crude synthetic drug using upright coil planet centrifuge with four multilayer coils connected in series. J Chromatogr A. 2005 May 27;1076(1-2):207-11. PubMed PMID: 15974091.
9: Randall S. Valrubicin: an alternative to radical cystectomy for carcinoma in situ of the bladder. Urol Nurs. 2001 Feb;21(1):30-1, 34-6. Review. PubMed PMID: 11998112.
10: Kuznetsov DD, Alsikafi NF, O'Connor RC, Steinberg GD. Intravesical valrubicin in the treatment of carcinoma in situ of the bladder. Expert Opin Pharmacother. 2001 Jun;2(6):1009-13. Review. PubMed PMID: 11585003.