PT  - JOURNAL ARTICLE
AU  - Ronald E. Savage
AU  - Andrew N. Tyler
AU  - Xiu-Sheng Miao
AU  - Thomas C. K. Chan
TI  - Identification of a Novel Glucosylsulfate Conjugate as a Metabolite of 3,4-Dihydro-2,2-dimethyl-2<em>H</em>-naphtho[1,2-<em>b</em>]pyran-5,6-dione (ARQ 501, β-Lapachone) in Mammals
AID  - 10.1124/dmd.107.018655
DP  - 2008 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 753--758
VI  - 36
IP  - 4
4099  - http://dmd.aspetjournals.org/content/36/4/753.short
4100  - http://dmd.aspetjournals.org/content/36/4/753.full
SO  - Drug Metab Dispos2008 Apr 01; 36
AB  - 3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (ARQ 501) is a fully synthetic version of the natural product β-lapachone, which has been isolated from the lapacho tree (Tabebuia impetiginosa or Tabebuia avellanedae) and has demonstrated promising anticancer activity. ARQ 501 formulated with hydroxypropyl-β-cyclodextrin has successfully completed phase I clinical trials and is currently in several phase II human clinical trials for the treatment of pancreatic cancer, head and neck cancer, and leiomyosarcoma. The metabolites of ARQ 501 were investigated by low-resolution and high-resolution mass spectrometry in plasma from (nu/nu) mice, rats, and humans treated with the compound. The data for one of the metabolites identified are consistent with conjugation of ARQ 501 with a glucosylsulfate moiety (m/z 241; fragment ion). Although other glucosylsulfate conjugates have been identified as metabolites of pesticides in cotton plants and in crustaceans as phase II metabolites of pyrenes, none have been previously identified in mammals. Data reported here identify a novel metabolic pathway for humans.