Amonafide

Description

Biological Activity

Protocol(Only for Reference)

Clinical Trial Information( data from http://clinicaltrials.gov)

Chemical Information

Cell Assay: ^[5]

References

貨號 Cat. No.: S1367
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Amonafide

Catalog No.S1367

Amonafide produces protein-associated DNA-strand breaks through a topoisomerase II-mediated reaction, but does not produce topoisomerase I-mediated DNA cleavage. Phase 3.

Size

Price

Stock

Quantity

10mM/1mLIn DMSO	USD 201	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 151	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 466	In stock	0 1 2 3 4 5 6 7 8 9 10
100mg	USD 844	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Cell lines	HT-29, HeLa, and PC3
Concentrations	Dissolved in DMSO, final concentrations ~10 μM
Incubation Time	72 hours
Method	All cell lines are in the logarithmic phase of growth when the assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is carried out. Cells are harvested and seeded into 96-well tissue culture plates at a density of 2.5 × 10³ cells/well in 150 μL aliquots of medium. The concentrations tested are serial dilutions of a stock solution (10 μM in DMSO) with phosphate-buffered saline (PBS) and are added 24 hours later. The assay is ended after 72 hours of Amonafide exposure and PBS is used as a negative control. After 72 hours treatment, cells are washed twice with PBS, and then 50 μL/well of MTT reagent (1 mg/mL in PBS) together with 150 μL/well of prewarmed medium are added. The plates are returned to the incubator for 4 hours. Subsequently, DMSO is added as solvent. Absorbance is determined at 570 nm with a Microplate reader. All experiments are performed at least three times, and the average of the percentage absorbance is plotted against concentration. Then, the concentration of Amonafide required to inhibit 50% of cell growth (IC50) is calculated for Amonafide.

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT00074100	Completed	Breast Cancer	National Cancer Institute (NCI)\|Memorial Sloan-Kettering Cancer Center	2003-08	Phase 2
NCT00087854	Completed	Prostate Cancer	Xanthus Pharmaceuticals, Inc.	2004-03	Phase 1\|Phase 2
NCT00273884	Completed	Acute Myeloid Leukemia	Xanthus Pharmaceuticals, Inc.	2005-08	Phase 2
NCT00715637	Active, not recruiting	Secondary Acute Myeloid Leukemia (Secondary AML, sAML)	Antisoma Research	2007-06	Phase 3
NCT01066494	Active, not recruiting	Acute Myeloid Leukemia	Antisoma Research	2010-01	Phase 2

Description

Amonafide produces protein-associated DNA-strand breaks through a topoisomerase II-mediated reaction, but does not produce topoisomerase I-mediated DNA cleavage. Phase 3.

Topoisomerase II

In vitro

Through a topoisomerase II-mediated reaction, Amonafide treatment produces DNA single-strand breaks (SSB), double-strand breaks (DSB), and DNA-protein cross-links in human myeloid leukemia cells. Amonafide treatment inhibits conlony formation of the leukemic cell lines and the normal human bone marrow GM-CFC in a dose-dependent manner. Amonafide does not produce topoisomerase I-mediated DNA cleavage even at 100 μM. The m-AMSA-resistant line is less than 2-fold resistant to Amonafide ^[1] Amonafide interferes with the DNA breakage-reunion activity of mammalian DNA topoisomerase II resulting in DNA cleavage stimulation. ^[2]Compared with those of other antitumor drugs, Amonafide-stimulated cleavage intensity patterns are markedly different. Amonafide highly prefers a cytosine, and excludes guanines and thymines instead, at position -1, with lower preference for an adenine at position +1. ^[3] Topoisomerase II-mediated DNA cleavage induced by Amonafide is affected only slightly (less than 3-fold) by 1 mM ATP, suggeting that Amonafide is an ATP-insensitive topoisomerase II inhibitor in contrast to doxorubicin, etoposide, and mitoxantrone. ^[4] Amonafide significantly inhibits the growth of HT-29, HeLa, and PC3 cells with IC50 of 4.67 μM, 2.73 μM, and 6.38 μM, respectively. ^[5] Amonafide is unaffected by P-glycoprotein-mediated efflux, unlike those of the classical topoisomerase II inhibitors (daunorubicin, doxorubicin, idarubicin, etoposide, and mitoxantrone). ^[6]

Download Amonafide SDF

Molecular Weight (MW)	283.33
Formula	C₁₆H₁₇N₃O₂
CAS No.	69408-81-7

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	AS1413, Xanafide, Quinamed

Solubility (25°C) *	In vitro	DMSO	57 mg/mL (201 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	4 mg/mL (14 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.