N-Trifluoroacetyladriamycin | CAS#26295-56-7 | metabolite of valrubicin

MedKoo Cat#: 597592 | Name: N-Trifluoroacetyladriamycin

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Description:

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

N-Trifluoroacetyladriamycin is a metabolite of valrubicin. 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.

Chemical Structure

N-Trifluoroacetyladriamycin

CAS#26295-56-7

Theoretical Analysis

MedKoo Cat#: 597592

Name: N-Trifluoroacetyladriamycin

CAS#: 26295-56-7

Chemical Formula: C29H28F3NO12

Exact Mass: 639.1564

Molecular Weight: 639.53

Elemental Analysis: C, 54.46; H, 4.41; F, 8.91; N, 2.19; O, 30.02

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 510.00

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Synonym

N-Trifluoroacetyladriamycin; NSC 283464; NSC-283464; NSC283464; AD 41; AD-41; AD41;

IUPAC/Chemical Name

2,2,2-trifluoro-N-((2S,3S,4S,6R)-3-hydroxy-2-methyl-6-(((3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl)oxy)tetrahydro-2H-pyran-4-yl)acetamide

InChi Key

RQIOYWADAKTIJC-QFVZNODKSA-N

InChi Code

InChI=1S/C29H28F3NO12/c1-10-22(36)13(33-27(41)29(30,31)32)6-17(44-10)45-15-8-28(42,16(35)9-34)7-12-19(15)26(40)21-20(24(12)38)23(37)11-4-3-5-14(43-2)18(11)25(21)39/h3-5,10,13,15,17,22,34,36,38,40,42H,6-9H2,1-2H3,(H,33,41)/t10-,13-,15?,17-,22+,28-/m0/s1

SMILES Code

C[C@H]1[C@@H](O)[C@@H](NC(C(F)(F)F)=O)C[C@H](OC2C[C@@](C(CO)=O)(O)Cc3c(O)c(C(c4c(C5=O)c(OC)ccc4)=O)c5c(O)c32)O1

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

>3 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).

HS Tariff Code

2934.99.03.00

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

N-Trifluoroacetyladriamycin is a metabolite of valrubicin.

In vitro activity:

Valrubicin's mode of action in keratinocytes was investigated by studying its possible effect on PKCα activation. PKCα's characteristic to translocate from the cytoplasm to the cellular membrane when activated was assessed by measuring the amount of PKCα in the soluble and membrane-bound protein fractions isolated from valrubicin stimulated keratinocytes and by visualizing PKCα in stimulated cells over time. Downstream signaling was investigated by measuring the amount of phosphorylated Myristoylated Alanine-rich C-kinase substrate (MARCKS) and extracellular signal-regulated kinases (ERK) 1/2 of valrubicin-stimulated keratinocytes. The results indicated that valrubicin activates PKCα in vitro as shown by PKCα's translocation and phosphorylation of downstream signaling molecules. Reference: J Drugs Dermatol. 2013 Oct;12(10):1156-62. https://jddonline.com/articles/dermatology/S1545961613P1156X

In vivo activity:

The effect of treating psoriasis with a daily topical application of valrubicin cream was investigated in a psoriasis xenograft transplantation model. In vivo, valrubicin treatment resulted in a normalization of epidermal morphology and a reduction in epidermal thickness after 12 days. In addition, the dermal vessel pattern was reduced and the stratum granulosum was regained. Staining for a regenerative proliferation marker showed a decrease in keratinocyte proliferation, and scattered epidermal cells showed apoptosis. These results indicated that valrubicin successfully treats psoriasis in a xenograft transplantation model, suggesting that topical valrubicin may become an upcoming treatment for psoriasis. Reference: J Invest Dermatol. 2010 Feb;130(2):455-63. https://www.jidonline.org/article/S0022-202X(15)34692-3/fulltext

Preparing Stock Solutions

The following data is based on the product molecular weight 639.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Laugesen IG, Hauge E, Andersen SM, Stenderup K, de Darkó 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;12(10):1156-62. PMID: 24085052. 2. Rosada C, Stenderup K, de Darkó 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. PMID: 19741712.

In vitro protocol:

In vivo protocol:

1. Rosada C, Stenderup K, de Darkó 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. PMID: 19741712.

1: Krishan A, Dutt K, Israel M, Ganapathi R. Comparative effects of adriamycin and N-trifluoroacetyladriamycin-14-valerate on cell kinetics, chromosomal damage, and macromolecular synthesis in vitro. Cancer Res. 1981 Jul;41(7):2745-50. PubMed PMID: 6972801. 2: Chuang RY, Chuang LF, Kawahata RT, Israel M. Effect of N-trifluoroacetyladriamycin-14-valerate on [3H]thymidine uptake and DNA synthesis of human lymphoma cells. J Biol Chem. 1983 Jan 25;258(2):1062-5. PubMed PMID: 6822492. 3: Israel M, Modest EJ, Frei E 3rd. N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin. Cancer Res. 1975 May;35(5):1365-8. PubMed PMID: 1054622. 4: Sweatman TW, Parker RF, Israel M. Pharmacologic rationale for intravesical N-trifluoroacetyladriamycin-14-valerate (AD 32): a preclinical study. Cancer Chemother Pharmacol. 1991;28(1):1-6. PubMed PMID: 2040028. 5: Zirvi KA, Gilani SH, Hill GJ. Embryotoxic effects of doxorubicin and N-trifluoroacetyladriamycin-14-valerate (AD-32). Teratology. 1985 Apr;31(2):247-52. PubMed PMID: 3992493. 6: Niell HB, Hunter RF, Herrod HG, Israel M. Effects of N-trifluoroacetyladriamycin-14-valerate (AD-32) on human bladder tumor cell lines. Cancer Chemother Pharmacol. 1987;19(1):47-52. PubMed PMID: 3815726. 7: Brox L, Gowans B, Belch A. N-trifluoroacetyladriamycin-14-valerate and adriamycin induced DNA damage in the RPMI-6410 human lymphoblastoid cell line. Can J Biochem. 1980 Sep;58(9):720-5. PubMed PMID: 7006761. 8: Israel M, Wilkinson PM, Pegg WJ, Frei E 3rd. Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat. Cancer Res. 1978 Feb;38(2):365-70. PubMed PMID: 620407. 9: Facchinetti T, Raz A, Goldman R. A differential interaction of daunomycin, adriamycin, and N-trifluoroacetyladriamycin 14-valerate with mouse peritoneal macrophages. Cancer Res. 1978 Nov;38(11 Pt 1):3944-9. PubMed PMID: 212183. 10: Marsh JC. Comparison of the sensitivities of human, canine, and murine hematopoietic precursor cells to adriamycin and N-trifluoroacetyladriamycin-14-valerate. Cancer Res. 1979 Feb;39(2 Pt 1):360-4. PubMed PMID: 761207. 11: Chuang LF, Kung HF, Israel M, Chuang RY. Activation of human leukemia protein kinase C by tumor promoters and its inhibition by N-trifluoroacetyladriamycin-14-valerate (AD 32). Biochem Pharmacol. 1992 Feb 18;43(4):865-72. PubMed PMID: 1540240. 12: Kanter PM, Schwartz HS. Effects of N-trifluoroacetyladriamycin-14-valerate and related agents on DNA strand damage and thymidine incorporation in CCRF-CEM cells. Cancer Res. 1979 Feb;39(2 Pt 1):448-51. PubMed PMID: 761217. 13: Parker LM, Hirst M, Israel M. N-trifluoroacetyladriamycin-14-valerate: additional mouse antitumor and toxicity studies. Cancer Treat Rep. 1978 Jan;62(1):119-27. PubMed PMID: 272230. 14: Chuang LF, Kawahata RT, Chuang RY. Inhibition of chicken myeloblastosis RNA polymerase II activity in vitro by N-trifluoroacetyladriamycin-14-valerate. FEBS Lett. 1980 Aug 11;117(1):247-51. PubMed PMID: 7409170. 15: Potmesil M, Israel M, Kirschenbaum S, Bowen J, Silber R. Effects of N-trifluoroacetyladriamycin-14-O-hemiadipate and radiation on L1210 cells. Radiat Res. 1986 Feb;105(2):147-57. PubMed PMID: 3754052. 16: Vecchi A, Cairo M, Mantovani A, Sironi M, Spreafico F. Comparative antineoplastic activity of adriamycin and N-trifluoroacetyladriamycin-14-valerate. Cancer Treat Rep. 1978 Jan;62(1):111-7. PubMed PMID: 626989. 17: Abbruzzi R, Rizzardini M, Benigni A, Barbieri B, Donelli MG, Salmona M. Possible relevance of N-trifluoroacetyladriamycin (AD 41) in the antitumoral activity of N-trifluoroacetyladriamycin-14-valerate (AD 32) in tumor-bearing mice. I. Pharmacokinetic evidence. Cancer Treat Rep. 1980 Aug-Sep;64(8-9):873-8. PubMed PMID: 7448825. 18: Blum RH, Garnick MB, Israel M, Canellos GP, Henderson IC, Frei E 3rd. Initial clinical evaluation of N-trifluoroacetyladriamycin-14-valerate (AD-32), an adriamycin analog. Cancer Treat Rep. 1979 May;63(5):919-23. PubMed PMID: 455334. 19: Lameh J, Chuang RY, Israel M, Chuang LF. Nucleoside uptake and membrane fluidity studies on N-trifluoroacetyladriamycin-14-O-hemiadipate-treated human leukemia and lymphoma cells. Cancer Res. 1989 Jun 1;49(11):2905-8. PubMed PMID: 2541896. 20: Chuang LF, Israel M, Chuang RY. Inhibition of the initiation of leukemic transcription by N-trifluoroacetyladriamycin-14-O-hemiadipate in vitro. Impaired formation of RNA polymerase-DNA complex. J Biol Chem. 1984 Sep 25;259(18):11391-5. PubMed PMID: 6206068.