Berubicin Hydrochloride
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| Category | Antineoplastic |
| Catalog number | BBF-05864 |
| CAS | 293736-67-1 |
| Molecular Weight | 670.10 |
| Molecular Formula | C34H35NO11.HCl |
| Purity | ≥95% |
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Description
Berubicin hydrochloride is the hydrochloride of berubicin, which is an anthracycline derivative used as a topoisomerase II inhibitor with activity in ependymoma. Berubicin hydrochloride has potential antineoplastic activity.
Specification
| Related CAS | 677017-23-1 (free base) |
| Synonyms | Daunorubicin Impurity 9 hydrochloride; RTA 744 hydrochloride; WP 769 hydrochloride; 5,12-Naphthacenedione, 10-[[3-amino-2,3,6-trideoxy-4-O-(phenylmethyl)-α-L-lyxo-hexopyranosyl]oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, (8S,10S)-, hydrochloride (1:1) |
| Shelf Life | As supplied, 2 years from the QC date provided on the Certificate of Analysis, when stored properly. |
| Storage | Store at -20°C |
| IUPAC Name | (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-6-methyl-5-phenylmethoxyoxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride |
| Canonical SMILES | CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)OCC6=CC=CC=C6.Cl |
| InChI | InChI=1S/C34H35NO11.ClH/c1-16-33(44-15-17-7-4-3-5-8-17)20(35)11-24(45-16)46-22-13-34(42,23(37)14-36)12-19-26(22)32(41)28-27(30(19)39)29(38)18-9-6-10-21(43-2)25(18)31(28)40;/h3-10,16,20,22,24,33,36,39,41-42H,11-15,35H2,1-2H3;1H/t16-,20-,22-,24-,33+,34-;/m0./s1 |
| InChI Key | GPMIHHFZKBVWAZ-LMMKTYIZSA-N |
Properties
| Appearance | Solid powder |
| Application | A topoisomerase II inhibitor with activity in ependymoma. |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Solubility | Soluble in DMSO |
Reference Reading
1.Nuclear factor-kappa B and apoptosis inducing factor activation by doxorubicin analog WP744 in SH-SY5Y neuroblastoma cells.
Wu J;Harris NL;Inge TH J Surg Res. 2004 Dec;122(2):231-9.
BACKGROUND: ;Neuroblastoma (NB) is one of the most common extracranial tumors in children. The chemotherapeutic doxorubicin (Dox) remains a mainstay for treatment. However, the emergence of drug resistance seriously limits treatment efficacy. Numerous Dox analogues have been designed to more potently kill drug naive as well as drug-resistant NB. We have shown that the Dox analogue WP744 has enhanced the killing activity of NB compared to Dox, but the mechanism(s) of action is unclear.;MATERIALS AND METHODS: ;MTT assays were used to characterize the relative potencies of Dox and WP744 against SH-SY5Y NB cells. Western blotting was used to assess activation of caspases-3, -9, anti-poly (ADP-ribose) polymerase, p53, p21, AIF, IkappaBalpha, Bcl-2, Bcl-X(L), and cyclin D1. Nuclear factor (NF-kappaB) activation was assessed by electrophoretic mobility shift assay.;RESULTS: ;After WP744 treatment, enhanced apoptosis and cell death were seen, associated with cleavage of caspases-3, -9, and anti-poly (ADP-ribose) polymerase, an increase in p53 protein levels, and the induction of p21. WP744 also induced translocation of apoptosis-inducing factor from mitochondria to nuclei. Most remarkably, WP744 was 50-fold more potent than Dox in activating NF-kappaB.
2.Evidence that activation of nuclear factor-kappaB is essential for the cytotoxic effects of doxorubicin and its analogues.
Ashikawa K;Shishodia S;Fokt I;Priebe W;Aggarwal BB Biochem Pharmacol. 2004 Jan 15;67(2):353-64.
Several reports within the last 5 years have suggested that nuclear factor (NF)-kappaB activation suppresses apoptosis through expression of anti-apoptotic genes. In the present report, we provide evidence from four independent lines that NF-kappaB activation is required for the cytotoxic effects of doxorubicin. We used doxorubicin and its structural analogues WP631 and WP744, to demonstrate that anthracyclines activate NF-kappaB, and this activation is essential for apoptosis in myeloid (KBM-5) and lymphoid (Jurkat) cells. All three anthracyclines had cytotoxic effects against KBM-5 cells; analogue WP744, was most potent, with an IC(50) of 0.5 microM, and doxorubicin was least active, with an IC(50) of 2 microM. We observed maximum NF-kappaB activation at 1 microM with WP744 and at 50 microM with doxorubicin and WP631, and this activation correlated with the IkappaBalpha degradation. Because the anthracycline analogue (WP744), most active as a cytotoxic agent, was also most active in inducing NF-kappaB activation and the latter preceded the cytotoxic effects, suggests that NF-kappaB activation may mediate cytotoxicity. Second, receptor-interacting protein-deficient cells, which did not respond to doxorubicin-induced NF-kappaB activation, were also protected from the cytotoxic effects of all the three anthracyclines.
3.The 4'-O-benzylated doxorubicin analog WP744 overcomes resistance mediated by P-glycoprotein, multidrug resistance protein and breast cancer resistance protein in cell lines and acute myeloid leukemia cells.
Brooks TA;O'Loughlin KL;Minderman H;Bundy BN;Ford LA;Vredenburg MR;Bernacki RJ;Priebe W;Baer MR Invest New Drugs. 2007 Apr;25(2):115-22. Epub 2006 Oct 28.
BACKGROUND: ;The synthetic 4'-O-benzylated doxorubicin analog WP744 was designed to abrogate transport by the multidrug resistance (MDR)-associated ATP-binding cassette (ABC) proteins P-glycoprotein (Pgp) and multidrug resistance protein (MRP-1). We compared its uptake and cytotoxicity with those of doxorubicin and daunorubicin in cell lines overexpressing Pgp, MRP-1 or breast cancer resistance protein (BCRP) and in acute myeloid leukemia (AML) cells.;METHODS: ;Cellular uptake was studied by flow cytometry and cytotoxicity in 96-h 96-well cultures in cell lines overexpressing Pgp, MRP-1 or wild type (BCRP(R482)) or mutant (BCRP(R482T), BCRP(R482G)) BCRP and in pre-treatment AML marrow cells.;RESULTS: ;Uptake and cytotoxicity of WP744 were consistently greater than those of doxorubicin and daunorubicin at equimolar concentrations in all cell lines studied and in AML cells.;CONCLUSION: ;WP744 overcomes transport by Pgp, MRP-1 and BCRP in cell lines and AML cells and is a promising agent for clinical development in AML and other malignancies with broad-spectrum multidrug resistance.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
