Disease relevance of LOBUCAVIR

• Interestingly, the ED50 value of (R)-BHCG is about 100-fold higher against HCMV than against HSV-1, and the relative levels of (R)-BHCG triphosphate formed in cells infected by the two viruses are roughly proportional to the antiviral activities [1].
• In plaque reduction assays, (R)-BHCG was about 1000 times more active than its S-enantiomer on herpes simplex virus type I (HSV-1) and over 200 times more active against a thymidine kinase-deficient mutant HSV-1 and human cytomegalovirus (HCMV) [1].
• Both cyclobut-A and cyclobut-G protected CD4+ ATH8 cells against the infectivity and cytopathic effect of HIV type 1 (HIV-1) and suppressed proviral DNA synthesis in ATH8 cells exposed to HIV-1 in vitro at concentrations of 50 to 100 microM [2].
• Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice [3].
• SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection [3].

High impact information on LOBUCAVIR

• Metabolic studies using HCMV-infected cells showed only a small degree of phosphorylation of (R)-BHCG and none of (S)-BHCG [1].
• We now show that both (R)-BHCG and (S)-BHCG are efficiently phosphorylated to their mono-, di-, and triphosphates by HSV-1-infected cells, in a manner similar to that of acyclovir [Proc. Natl. Acad. Sci. USA 74:5716-5720 (1977)] [1].
• Newer options, such as oral ganciclovir, cidofovir, benzimidavir (1263W94) and lobucavir, are currently under investigation and might further improve the management of CMV infection in recipients of solid-organ or stem-cell transplants [4].
• In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir [5].
• Lobucavir is phosphorylated in human cytomegalovirus-infected and -uninfected cells and inhibits the viral DNA polymerase [6].

Chemical compound and disease context of LOBUCAVIR

• Valaciclovir is also being developed for the prevention of CMV infections and famciclovir and lobucavir for the treatment of hepatitis B virus infection [7].
• Cyclobut-A and cyclobut-G, carbocyclic oxetanocin analogs that inhibit the replication of human immunodeficiency virus in T cells and monocytes and macrophages in vitro [2].
• Patients with persistent elevation of serum tumor markers (AFP, BHCG, and LDH) following orchiectomy, stage T2-T4 primary tumors, any evidence of metastases and pure choriocarcinoma or pure seminoma on histology were excluded from study [8].
• Efficiency of phosphorylation of the cyclobut-G (A-69992) enantiomers by HSV-1 thymidine kinase does not correlate with their anti-herpesvirus activity [9].
• In this work, we investigated the anti-hepatitis B virus (HBV) activity of lamivudine, adefovir, tenofovir, penciclovir and lobucavir after short-term (i.e. 24 or 48 h) or continuous (9 days) exposure of the HBV-containing cell line, HepG2 2.2.15, to these drugs [10].

Biological context of LOBUCAVIR

• In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion [3].
• Although both cyclobut-A and cyclobut-G appear to have a certain level of in vitro toxicity, our observations may have theoretical and clinical implications in understanding the structure-activity relationships of antiretroviral agents active against HIV [2].
• Regioselective enzymatic aminoacylation of lobucavir to give an intermediate for lobucavir prodrug [11].

Anatomical context of LOBUCAVIR

• Prognostic value of BHCG and local tumor invasion in stage I seminoma of the testis [12].

Associations of LOBUCAVIR with other chemical compounds

• The regional absorption of lobucavir (LBV), an experimental antiviral agent, and ganciclovir (DHPG) was investigated in rabbit intestine using an in situ single-pass perfusion technique [13].
• Elevated AFP and BHCG levels provide prognostic information at diagnosis, indicate persistent disease following orchiectomy or RPLND, and signal a recurrence after chemotherapy [14].
• Future investigations may furthermore help to clarify the role of novel antiviral agents, such as cidofovir, lobucavir, and compound 1263W94, and of the adoptive immunotherapy with virus-specific CTL clones in severely immunodeficient cancer patients [15].

Gene context of LOBUCAVIR

• Changes in EPA in sera of lobucavir treated animals were comparable to changes in WHV DNA levels [16].
• The increasing use of quantitative BHCG assay and vaginal ultrasonography have made early diagnosis possible, allowing conservative tubal surgery when indicated [17].
• Hence every female in reproductive age group with unexplained bleeding per vaginum should be investigated with serum BHCG (Beta human chorionic gonadotrophin) [18].

Analytical, diagnostic and therapeutic context of LOBUCAVIR

• The uterine cavity was evacuated by suction curettage after delivery and plasma, BHCG was negative 4 weeks subsequently [19].

References