Disease relevance of Bropirimine

• Mice treated with the IFN-inducing bropirimine [2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone] i.p. twice a week for 14 weeks starting on day 30 of start of FANFT feeding developed fewer transitional cell carcinomas (TCC) than mice treated with the vehicle [1].
• Bropirimine alone was marginally active against some experimental tumors such as B16 melanoma but was ineffective against others such as P388 or L1210 leukemia [2].
• The toxicity of bropirimine was minimal [3].
• PURPOSE: To evaluate bropirimine for in vivo activity in rodent prostate cancer [4].
• Treatment of carcinoma in situ of the urinary bladder with bropirimine [5].

High impact information on Bropirimine

• Relationship between modulation of natural killer cell activity and antitumor activity of bropirimine when used in combination with various types of chemotherapeutic drugs [2].
• Bropirimine (ABPP), a pyrimidinone, is currently under clinical trial for its antitumor potential [2].
• Imiquimod stimulated significantly higher levels of IFN when compared with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) and similar levels of IFN when compared with tilorone [6].
• Recombinant alpha interferon delta 4 alpha 1/alpha 2 (1 x 10(4) and 5 x 10(4) units per mouse per day) and bropirimine (100 and 300 mg/kg/day) provided no protection from the lethal MCMV infection [7].
• CONCLUSIONS: Bropirimine has statistically significant in vivo activity against both of these rodent prostate cancer cell lines [4].

Chemical compound and disease context of Bropirimine

• Several biological response modifiers administered orally such as vitamin A (and its derivatives), Lactobacillus casei or bropirimine have been tested in clinical trials as well [8].
• Effects of an interferon inducer bropirimine on bleomycin-induced lung fibrosis in hamsters [9].
• A phase II clinical trial of oral bropirimine in combination with intravesical bacillus Calmette-Guérin for carcinoma in situ of the bladder: a Southwest Oncology Group Study [10].

Biological context of Bropirimine

• In the present study, each of four groups of 5 bred rats and four groups of 10 bred rats was given bropirimine (gastric intubation) on Day 10 of gestation [11].
• Application of this method to the quantitation of bropirimine in rat plasma for a toxicokinetic/bioavailability study is reported [12].
• In this manuscript, we provide data gathered in attempts to further characterize the apparent requirement for S9 and understand the mechanism by which bropirimine induces chromosome aberrations [13].
• Comparative mutagenicity testing of bropirimine, 3. Bropirimine does not induce cytogenetic damage in vivo in the rat but does produce micronuclei in the mouse [14].
• Human biotransformation of bropirimine. Characterization of the major bropirimine oxidative metabolites formed in vitro [15].

Anatomical context of Bropirimine

• A subsequent experiment demonstrated the ability of bropirimine to induce HPRT mutations in CHO cells [16].
• Coincubation with the selective CYP1A2 inhibitor alpha-naphthoflavone abolished bropirimine metabolism in human liver microsomes [15].
• OBJECTIVES: Bropirimine is an oral immunomodulator that has demonstrated anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary tract [17].
• Twenty-four patients with negative radiographic findings and positive cytologic evidence for upper tract CIS in one or both ureters received bropirimine (3.0 g/day orally) for 3 consecutive days each week for up to 1 year [18].
• Pyrimidinone (bropirimine) mediated alteration of T lymphocyte subsets during murine cytomegalovirus infection [19].

Associations of Bropirimine with other chemical compounds

• 3. The activity of bropirimine O-glucuronidation by human liver microsomes was inhibited by bilirubin (40%) and with mefenamic acid (80%) [20].
• The disappearance of bropirimine from the small intestinal loop was suppressed by sodium glycocholate contained in the solution, because of the loss of thermodynamic activity of bropirimine after its involvement in the micellar complex, not by the direct effect of bile salt on the permeability of intestinal mucosa [21].
• Lack of interaction between bropirimine and 5-fluorouracil on human dihydropyrimidine dehydrogenase [22].
• The hamsters were randomized in four groups and treated with either bropirimine (100 mg/kg, intraperitoneally) suspended in carboxymethylcellulose (CMC, 10 mg/10 mg/ml) or CMC alone each day for sixteen days [9].
• METHOD: Bropirimine (400 mg/kg, p.o.) or rhIL-1 beta (20, 30, or 40 micrograms/kg, s.c.) was administered on gestation day 10 to Crl:CD[BR] (CD) or TUC rats, alone and in combination with progesterone (2 mg/kg/day, s.c.) or indomethacin (0.6 mg/day, s.c., days 9-11) [23].

Gene context of Bropirimine

• 4. The results demonstrate that UGT1A9 and to a lesser extent UGT1A1 are responsible for the majority of bropirimine O-glucuronidation in man [20].
• In vitro studies using human liver microsomes and recombinant cytochrome P450 isoforms were performed to identify the P450 enzyme(s) responsible for bropirimine oxidation [15].
• Perpheral blood mononuclear cells (PBMCs) obtained from five healthy volunteers were co-cultured with bropirimine and the levels of various cytokines, including IFN-alpha, gamma, IL-1beta and TNF-alpha in the supernatants, were quantified [24].
• Although buprenorphine extensively inhibited the activity of bropirimine O-glucuronidation by UGT1A3, the inhibition profile did not parallel that observed in HLMs [20].
• In murine severe experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis (MS), we tested the efficacy of a 5-halo-6-phenyl pyrimidinone compound, bropirimine (PNU-54461) [25].

Analytical, diagnostic and therapeutic context of Bropirimine

• Bropirimine was given on varying schedules at 250 mg./kg. by gavage, and tumor volume and survival were recorded [4].
• Further clinical trials of bropirimine in bladder cancer appear warranted [3].
• Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guérin [17].
• Antitumor effects of oral administration of an interferon-inducing pyrimidinone, Bropirimine, on murine renal-cell carcinoma [26].
• Assay of bropirimine in rat plasma by means of robotic solid-phase extraction and high-performance liquid chromatography [12].

References