Background:

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 treatment

of 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].

Clinical trial: Voreloxin showed an acceptable safety profile with clinical activity in patients with relapsed/refractory solid tumors. The maxmum tolerence dose was schedule-dependent. Voreloxin is now in clinical studies of ovarian cancer and acute myeloid leukemia [3].

参考文献:
[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.