Biological Activity
voreloxin, formerly known as sns-595 or ag-7352, is a novel naphthyridine analog, which is structurally related to the quinolone antibiotics, a chemical class not previously used for the treatmentof cancer.
in vitro
in vitro studies demonstrated voreloxin has broad anti-proliferative activity in 11 tumor cell lines, with ic50 values ranging from 0.04 to 0.97 μm. similar activity was observed in vitro in drug-resistant cell lines, including those that overexpress p-glycoprotein [2].
in vivo
after a single intravenous dose, voreloxin concentrations in tumor were correlated with induction of the apoptosis marker caspase-3. administration of voreloxin at 20 mg/kg weekly inhibited tumor growth (86%). voreloxin demonstrated strong dose-dependent tumor growth inhibition (63–88%) in 10 of 11 solid tumor xenograft models [2].
References
[1] tsuzuki y, tomita k, shibamori k, sato y, kashimoto s, chiba k. synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. part 2. j med chem. 2004;47(8):2097-109.
[2] hoch u, lynch j, sato y, kashimoto s, kajikawa f, furutani y, silverman ja. voreloxin, formerly sns-595, has potent activity against a broad panel of cancer cell lines and in vivo tumor models. cancer chemother pharmacol. 2009;64(1):53-65.
[3] advani rh, hurwitz hi, gordon ms, ebbinghaus sw, mendelson ds, wakelee ha, hoch u, silverman ja, havrilla na, berman cj, fox ja, allen rs, adelman dc. voreloxin, a first-in-class anticancer quinolone derivative, in relapsed/refractory solid tumors: a report on two dosing schedules. clin cancer res. 2010;16(7):2167-75.
