Antitumor activity and pharmacology of 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate: an orally active derivative of 1-beta-D-arabinofuranosylcytosine

Japanese Journal of Cancer Research : Gann
K KodamaM Saneyoshi

Abstract

The antitumor activity of 1-beta-D-arabinofuranosylcytosine-5'-alkylphosphates (CnPCAs) against L1210 leukemia in mice after oral administration was demonstrated. The optimum length of the alkyl group on the phosphate moiety of CnPCA for exhibiting a high antitumor activity was found to be between tetradecyl (C14) and tricosyl (C23). The most active alkyl derivative in this system was found to be 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate (C18PCA). The optimum and minimum effective doses of C18PCA were 100 and 6.25 mg/kg/day (q1d, day 1 to day 5), respectively. The maximum T/C% of C18PCA was approximately 220. The antitumor activity of C18PCA was not greatly dependent on the treatment schedule and route. Plasma concentration of 1-beta-D-arabinofuranosylcytosine (ara-C) remained in the range of 0.4 to 0.75 nmol/ml [corrected] for 24 h after oral administration of 100 mg/kg (170 mumol/kg) of C18PCA. These results indicate that C18PCA administered per orally is absorbed intact through the gastrointestinal tract and area-C is released of long period of time. C18PCA is regarded as an orally active depot form of ara-C.

References

Aug 1, 1976·Journal of Medicinal Chemistry·W J WechterG L Neil

❮ Previous
Next ❯

Citations

May 15, 2002·Archives of Pharmacal Research·Henry J LeeDong-Hoon Ko
Jan 30, 2008·International Journal of Hematology·Akira HorikoshiShigemasa Sawada
May 1, 1995·Antiviral Research·R J Jones, N Bischofberger
Mar 25, 2014·European Journal of Medicinal Chemistry·Chih-Yi ChangJing-Ping Liou
May 1, 1995·Medicinal Research Reviews·W J HoulihanS H Cheon
Nov 4, 2000·Medicinal Research Reviews·C R WagnerE J McIntee
Aug 7, 2002·Clinical Pharmacokinetics·Akinobu HamadaMasahiro Nakano

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.