Detail of "42228-92-2"

Reference

Inactivation by acivicin of carbamoyl phosphate synthetase II of human colon carcinoma

Inactivation by acivicin of carbamoyl phosphate synthetase II of human colon carcinoma. Sebolt, Judith S.; Aoki, Takashi; Eble, John N.; Glover, John L.; Weber, George (Sch. Med., Indiana Univ., Indianapolis, IN 46223, USA). Biochem. Pharmacol., 34(1), 97-100 (English) 1985. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 14 The effect of acivicin (I) [42228-92-2] (antitumor and antiglutamine drug) was detd. on the activity of the rate-limiting enzyme of de novo pyrimidine biosynthesis carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) (EC 6.3.5.5) [37233-48-0] in human colon carcinoma. The synthetase II activity in human colon carcinoma was elevated 2- to 3-fold over values of the normal colon mucosa, and the substrate kinetic consts. were similar for the enzyme in normal and neoplastic colon. The KM for L-glutamine [56-85-9] was 17 mM (colon carcinoma) and 23 mM (normal mucosa), whereas the KM for ATP [56-65-5] was 2.1 and 1.7 mM in tumor and mucosa, resp. The synthetase II activity in colon carcinoma was inhibited to a similar extent by UMP [58-97-9], UDP [58-98-0] and UTP [63-39-8] (36-41%). The 3 uracil nucleotides were also equally effective in inhibiting the enzyme from normal mucosa (39-46%). Both enzymes were activated by PRPP [7540-64-9] (63 and 7%) in mucosa and carcinoma, resp. Acivicin in vitro selectively inactivated the glutamine-dependent synthetase II from human colon carcinoma, and it did not affect the ammonia-dependent activity. The acivicin inactivation const. was 100 mM, and the min. inactivation half-time was 0.7 min. Acivicin most likely exerts its effect against human colon synthetase II by acting as an active site directed affinity analog of L-glutamine.

Drug sensitivity testing of carcinoma of the gallbladder and biliary tree in a human tumor cloning assay

Drug sensitivity testing of carcinoma of the gallbladder and biliary tree in a human tumor cloning assay. Harris, Gary J.; Von Hoff, Daniel D. (Health Sci. Cent., Univ. Texas, San Antonio, TX 78284, USA). Cancer Drug Delivery, 3(3), 197-204 (English) 1986. CODEN: CDDED7. ISSN: 0732-9482. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Tumor specimens from patients with carcinoma of the gallbladder and biliary tree were cultured. The specimens with evaluable growth yielded 44 drug tests, of which 27% resulted in ￡50% survival when compared to the untreated control plates. The std. chemotherapeutic agents carmustine [154-93-8], cis-platinum [15663-27-1], mitomycin C [50-07-7], and vinblastine [865-21-4], as well as the investigational agents mitoxantrone [65271-80-9], acronycine [7008-42-6], acivicin [42228-92-2], and methylglyoxal bisguanylhydrazone [459-86-9], demonstrated some in vitro activity and could be useful in carcinoma of the gallbladder and biliary tree. The human tumor cloning assay may be used to look for std. and investigational agents which should be tried against this relatively rare tumor.