Home DNA Damage/DNA Repair Topoisomerase inhibitor Beta-Lapachone For research use only.

Beta-Lapachone

Synonyms: β-Lapachone, ARQ-501

Beta-Lapachone (β-Lapachone, ARQ-501) is a selective DNA topoisomerase I inhibitor, exhibiting no inhibitory activities against DNA topoisomerase II or ligase. Phase 2.

Beta-Lapachone Chemical Structure

Beta-Lapachone Chemical Structure

CAS No. 4707-32-8

Purity & Quality Control

Beta-Lapachone Related Products

Signaling Pathway

Topoisomerase Signaling Pathways

Topoisomerase Signaling Pathway

Biological Activity

Description Beta-Lapachone (β-Lapachone, ARQ-501) is a selective DNA topoisomerase I inhibitor, exhibiting no inhibitory activities against DNA topoisomerase II or ligase. Phase 2.
Targets
Topo I [1] IDO1 [4]
0.44 μM
In vitro
In vitro Beta-Lapachone inhibits DNA relaxation induced by DNA topoisomerase I in a dose-dependent manner. [1] Treatment of beta-lapachone (100 nM or greater) results in >95% inhibition of Topo I DNA unwinding activity compared to the DMSO control. beta-lapachone (1-5 μM) causes a block in G0/G1 of the cell cycle and induces apoptosis by locking Topo I onto DNA and blocking replication fork movement in HL-60 and three human prostate cancer (DU-145, PC-3, and LNCaP) cells. [2] Beta-Lapachone facilitates the migration of mouse 3T3 fibroblasts and human endothelial EAhy926 cells through different MAPK signaling pathways, and thus accelerates scrape-wound healing in vitro. [3] In addition, beta-Lapachone inhibits purified recombinant IDO1 activity through uncompetitive inhibition with IC50 of 0.44 μM, and beta-lapachone also exhibits superior retention of intracellular IDO1 inhibitory activity with an IC50 of 1.0 μM, partially dependent on biotransformation by NQO1. [4] Beta-lapachone induces programmed necrosis of NQO1+ cancer cells by NQO1-dependent reactive oxygen species (ROS) formation and PARP1 hyperactivation. [5]
Kinase Assay Topoisomerase I Catalytic Actioity Assay [1]
Topoisomerase I Catalytic Actioity Assay: The enzymatic activity is analyzed by the DNA unwinding assay. DNA topoisomerase I, from TopoGEN (1 unit, which is defined as the amount of enzyme that converts 0.5 μg of superhelical DNA to the relaxed state in 30 minutes at 37 °C), is incubated with 0.5 μg of 6x174 RF DNA, in the presence or absence of Beta-Lapachone, in 20 μL of relaxation buffer (50 mM Tris (pH 7.5). 50 mM KCI, 10 mM MgCl2, 0.5 mM dithiothreitol, 0.5 mM EDTA, 30 μg/mL bovine serum albumin) for 30 minutes at 37 °C. Reactions are stopped by adding 1% SDS and proteinase K (50 μg/mL). After an additional 1-hour incubation at 37 °C, the products are separated by electrophoresis in 1% agarose gel in TAE buffer (0.04 M tris acetate, 0.001 M EDTA). The gel is stained with ethidium bromide after electrophoresis. The photographic negative is scanned with an NIH image analysis system.
Cell Research Cell lines HL-60, PC-3, DU145, and LNCaP cells
Concentrations 0.005 to 50 μM
Incubation Time 12 hours
Method IC50 calculations for each cell line are determined by DNA amount (IS) and anchorage-dependent colony formation (CF) assays. For the CF assay, cells are seeded at 500 viable cells/well in 6-well plates and incubated overnight, then treated with equal volumes of media containing beta-lapachone at final concentrations ranging from 0.005 to 50 μM in half-log increments (controls were treated with 0.25% DMSO, equivalent to the highest dose of beta-lapachonc used) for 4 hour or for continuous 12-hour exposures. Plates (3 wells/condition) are stained with crystal violet, and colonies of >50 normal-appearing cells are enumerated. IC50 values for various cells are calculated using drug doses with numbers of colonies surrounding 50% of control. For DNA assays, plates are harvested for IC50 determinations 8 days after treatment using a CytoFluor 2350 fluorescence measurement system. Six-well samplings are included in the calculation of DNA fluor units for each dose. A graph of beta-lapachone dose versus percentage control DNA in fluor units is used to calculate each IC50. All experiments are repeated at least twice, each in duplicate.
In Vivo
In vivo Beta-lapachone treatment (50 mg/kg) leads to potent inhibition of in vivo tumor growth in a xenograft mouse model of human ovarian cancer, and the combination of beta-lapachone and taxol produces a synergistic induction of apoptosis. [6] In normal and diabetic (db/db) mice, treatment of beta-lapachone results in a faster healing process than vehicle only. [3]
Animal Research Animal Models Human ovarian cancer cells (36M2) are established in nude mice.
Dosages 25–50 mg/kg
Administration Intraperitoneal administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00524524 Completed
Advanced Solid Tumors
ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)
 August 2007 Phase 1
NCT00622063 Completed
Cancer
ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)
 December 2006 Phase 1|Phase 2
NCT00358930 Completed
Head and Neck Neoplasms|Carcinoma Squamous Cell
ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)
 July 2006 Phase 2
NCT00102700 Completed
Pancreatic Cancer|Adenocarcinoma
ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)
 January 2005 Phase 2
NCT00099190 Completed
Carcinoma
ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)
 December 2004 Phase 1

Chemical Information & Solubility

Molecular Weight 242.27 Formula

C15H14O3
CAS No. 4707-32-8 SDF Download Beta-Lapachone SDF
Smiles CC1(CCC2=C(O1)C3=CC=CC=C3C(=O)C2=O)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 33 mg/mL ( (136.21 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 16 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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