Valrubicin

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.

Product information

CAS Number: 56124-62-0

Molecular Weight: 723.64

Formula: C34H36F3NO13

Synonym:

Valstar

Valtaxin

AD-32

Valrubicin

Related CAS Number:

26295-56-7 (N-Trifluoroacetyladriamycin)

80287-44-1 (Doxorubicin 14-valerate)

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

Smiles: C[C@@H]1O[C@@H](C[C@H](NC(=O)C(F)(F)F)[C@@H]1O)O[C@H]1C[C@@](O)(CC2=C1C(O)=C1C(C(=O)C3=CC=CC(OC)=C3C1=O)=C2O)C(=O)COC(=O)CCCC

InChiKey: ZOCKGBMQLCSHFP-PIXAVGEUSA-N

InChi: 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

Technical Data

Appearance: Red solid powder

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

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Valrubicin (AD 32) is a chemotherapy agent, inhibits TPA- and PDBu-induced PKC activation with IC50s of 0.85 and 1.25 μM, respectively. Valrubicin inhibits the binding of [3H]PDBu to PKC. Therefore, Valrubicin competes with the tumor promoter for the PKC binding site and prevents the latter from both interacting with the phospholipid and binding to PKC. Valrubicin shows cytotoxic activity against squamous cell carcinoma (SCC) cell line colony formation, with IC50s and IC90s of 8.24 ± 1.60 μM and 14.81 ± 2.82 μM for UMSCC5 cells, 15.90 ± 0.90 μM, 29.84 ± 0.84 μM for UMSCC5/CDDP‡ cells, and 10.50 ± 2.39 μM, 19.00 ± 3.91 μM for UMSCC10b cells, respectively. Moreover, Valrubicin in combination with radiation enhances the cytotoxicity.

In Vivo:

Valrubicin (3, 6, or 9 mg) reduces tumor growth at week 3 by intratumoral jection in hamster. Valrubicin (6 mg) combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) causes significant tumor shrinkage in hamster. Valrubicin (0.1 μg/μL) significantly reduces the number of infiltrating neutrophils in biopsies challenged with TPA at 24 h and attenuates chronic inflammation in mice. Valrubicin also decreases the expression levels of inflammatory cytokines in the acute model.

References:

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-Guérin. Urol Oncol. 2012 May 9. [Epub ahead of print] PubMed PMID: 22575238.
3. 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.
4. Steinberg GD, Smith ND, Ryder K, Strangman NM, Slater SJ. Factors affecting valrubicin response in patients with bacillus Calmette-Guérin-refractory bladder carcinoma in situ. Postgrad Med. 2011 May;123(3):28-34. doi: 10.3810/pgm.2011.05.2281. PubMed PMID: 21566413.

Products are for research use only. Not for human use.