133349-28-7

Upstream product

• 108-30-5 succinic acid anhydride 
• 104495-48-9 1-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-fluoropyrimidine-2,4(1H,3H)-dione 
• 40615-36-9 4,4'-dimethoxytrityl chloride 
• 50-91-9 5-Fluoro-2'-deoxyuridine 

Downstream Products

• 443751-31-3 thymidylyl(3'->5')P₁-thio-2'-deoxyadenylyl(3'->5')5-fluoro-2'-deoxyuridine 

Relevant academic research and scientific papers

A new class of 5-fluoro-2′-deoxyuridine prodrugs conjugated with a tumor-homing cyclic peptide CNGRC by ester linkers: Synthesis, reactivity, and tumor-cell-selective cytotoxicity

Purpose. Tumor-targeting prodrugs of 5-fluoro-2′-deoxyuridine (5-FdUrd), which are chemical conjugations of 5-FdUrd with a tumor-homing cyclic peptide CNGRC by succinate and glutarate linkers, were synthesized to investigate the structural effects of linkers on the hydrolytic release of 5-FdUrd and the tumor-cell-selective cytotoxicity. Methods. A solid phase synthesis method was used to produce 5-FdUrd prodrugs. The kinetics and efficiency of hydrolytic 5-FdUrd release from the prodrugs were investigated in phosphate buffer (PB), fetal bovine serum (FBS), HT-1080 cell lysate, MDA-MB-231 cell lysate, and MEM containing 10% FBS. The tumor-cell-selective cytotoxicity of prodrugs was evaluated by an MTT method. Results. Two tumor-targeting prodrugs CNF1 and CNF2 bearing 5-FdUrd conjugated with a common cyclic peptide CNGRC by succinate and glutarate linkers, respectively, and their control compounds CN1 and CN2 without 5-FdUrd moiety were synthesized and identified. CNF1 underwent hydrolysis to release 5-FdUrd more rapidly and efficiently than CNF2. Both prodrugs were of lower cytotoxicity compared to 5-FdUrd, showing more selective cytotoxicity toward APN/CD13 positive cells (HT-1080) than toward APN/CD13 negative cells (HT-29, MDA-MB-231). Conclusions. A new class of tumor-targeting 5-FdUrd prodrugs CNF1 and CNF2 were successfully synthesized. These prodrugs targeted a tumor marker APN/CD13 to cause tumor-cell-selective cyctotoxicity due to 5-FdUrd release, the rate of which could be controlled by the structure of ester linker.

THERAPEUTIC NANOCONJUGATES AND USES THEREOF

The present invention relates to nanostructured conjugates, more specifically to nanostructured fusion proteins suitable for the selective delivery of their conjugated therapeutic agents to specific cell and tissue types. It also relates to nanoparticles comprising such nanostructured proteins and the therapeutic uses thereof.

Selective targeting of 2′-deoxy-5-fluorouridine to urokinase positive malignant cells in vitro

A urokinase targeting conjugate of 2′-deoxy-5-fluorouridine (5-FUdr) was synthesized and tested for tumor-cell selective cytotoxicity in vitro. The 5-FUdr prodrug 2′-deoxy-5-fluoro-3′-O-(3-carboxypropanoyl)uridine (5-FUdrsuccOH) containing an ester-labile

Synthesis and enzymatic characterization of P1-thio-P2-oxo trideoxynucleoside diphosphates having AZT, FdU, or dT at the 3'-position

Model compounds for oligonucleotide-prodrugs, P1-thio-P2-oxo-tri-deoxyribonucleoside diphosphates: d[G5C0X] and d[TsA0X] (X = AZT, FdU or dT) have been prepared, and their hydrolyses by snake venom phosphodiesterase and nuclease S1 are described.

In vitro and in vivo antitumor activity of immunoconjugates prepared by linking 5-Fluorouridine to antiadenocarcinoma monoclonal antibody

5-Fluorouridine (5-FUr), a cytotoxic antitumoral agent not in clinical use because of its systemic toxicity, and AR-3, a monoclonal antibody specific to a human colorectal adenocarcinoma, were covalently linked via two different strategies. 5-FUr was 5' succinilated after protection of the secondary hydroxyl groups and the carboxylate derivative was then activated as N- hydroxysuccinimidyl ester in order to react with the amino groups present in the monoclonal antibody, giving an amide linkage. Alternatively, a 5-FUr immunoconjugate containing an acid-clearable hydrazone bond was formed from the reaction between an acyl hydrazide derivative of 5-FUr and a periodate oxydized antibody with approximately 12 aldehyde groups in its carbohydrate region. An average of 9 to 12 drug molecules were attached to the antibody. In a cytotoxic assay on the human colorectal carcinoma cell line HT-29, the hydrazone containing drug conjugate was equally active as the succinylamido conjugate and the free drug. However, ELISA showed that while in the case of the succinylamido conjugate the Mab immunoreactivity was not affected after conjugation, there was a significant loss of reactivity in the acid cleavable conjugate. In a model of a disseminated intraabdominal carcinomatosis by HT-29 intraperitoneal graft in nude mice, the 5-FUr immunoconjugate selected was more effective than the unconjugated drug in medium-term therapy (21 days after the graft and 16 days after drug treatment), albeit in the longer period the efficacy of the two formulations was similar. The toxic effect of the drug-conjugate in vivo was much weaker, demonstrating its clear advantage over the drug, in terms of pharmacological efficacy.