Imaging Pharmacodynamics of the α-Folate Receptor–Targeted Thymidylate Synthase Inhibitor BGC 945
نویسندگان
چکیده
منابع مشابه
Targeted Thymidylate Synthase Inhibitor BGC 945 − - Folate Receptor α Imaging Pharmacodynamics of the Updated
The assessment of tissue-specific pharmacodynamics is desirable in the development of tumor-targeted therapies. Plasma deoxyuridine (dUrd) levels, a measure of systemic thymidylate synthase (TS) inhibition, has limited application for studying the pharmacodynamics of novel TS inhibitors targeted to the high affinity A-folate receptor (FR). Here, we have evaluated the utility of [F]fluorothymidi...
متن کاملBGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors.
BGC 945 is a cyclopenta[g]quinazoline-based, thymidylate synthase inhibitor specifically transported into alpha-folate receptor (alpha-FR)-overexpressing tumors. Affinity of BGC 945 for the alpha-FR is 70% of the high-affinity ligand folic acid. In contrast to conventional antifolates, BGC 945 has low affinity for the widely expressed reduced-folate carrier (RFC). The K(i) for isolated thymidyl...
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The DNA nucleotide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive methylation of deoxyuridylate using the cofactor methylene-tetrahydrofolate (CH(2)H(4)folate). Most organisms, including humans, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, including all Rickettsia and other pathogens, use an altern...
متن کاملFolate-based thymidylate synthase inhibitors as anticancer drugs.
The enzyme, thymidylate synthase (TS) is considered an important target for the development of new anticancer agents. Moreover, the folate-binding site in TS is believed to offer better opportunities for the design of highly specific inhibitors than the pyrimidine (dUMP) binding site. This belief led to the design of N10-propargyl-5,8-dideazafolic acid (CB3717), a quinazoline-based drug which h...
متن کاملPolymorphisms in the reduced folate carrier, thymidylate synthase, or methionine synthase and risk of colon cancer.
Folate metabolism supports the synthesis of nucleotides as well as the transfer of methyl groups. Polymorphisms in folate-metabolizing enzymes have been shown to affect risk of colorectal neoplasia and other malignancies. Using data from a population-based incident case-control study (1,600 cases and 1,962 controls), we investigated associations between genetic variants in the reduced folate ca...
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ژورنال
عنوان ژورنال: Cancer Research
سال: 2008
ISSN: 0008-5472,1538-7445
DOI: 10.1158/0008-5472.can-08-0135