Disease relevance of 3'-Aminothymidine

• Solid-state and solution conformation of 3'-amino-3'-deoxythymidine, precursor to a noncompetitive inhibitor of HIV-1 reverse transcriptase [1].
• Effect of 3'-amino-3'-deoxythymidine on L1210 and P388 leukemias in mice [2].
• The clinical significance of these findings is unknown but toxicity may be increased if a decreased formation of GZDV is accompanied by shunting of metabolism to 3'-amino-3'-deoxythymidine which is alleged to be cytotoxic [3].

High impact information on 3'-Aminothymidine

• 3'-Amino-3'-deoxythymidine, the principal hydrolysis product of 3'-CTNU, was found to be an inhibitor of BCNU-stimulated ADPRP activity with potency similar to dThd [4].
• In addition to unchanged drug and its 5'-O-glucuronide (zidovudine glucuronide), two novel catabolites of zidovudine were detected as 3'-amino-3'-deoxythymidine (AMT), and its 5'-O-glucuronide (GAMT) [5].
• Investigation of the kinetics of decomposition in aqueous systems demonstrated that the primary UV-absorbing decomposition product is 3'-amino-3'-deoxythymidine and that only a limited amount of the compound is formed (less than 8%) [6].
• Role of human liver P450s and cytochrome b5 in the reductive metabolism of 3'-azido-3'-deoxythymidine (AZT) to 3'-amino-3'-deoxythymidine [7].
• The monophosphate derivative of 3'-amino-3'-deoxythymidine (AMT), an in vivo toxic catabolite of AZT, was the most potent of the ddN-MP analogs tested, inhibiting this activity by more than 50% at 100 microM [8].

Biological context of 3'-Aminothymidine

• After intravenous (i.v.) and oral dosing with either 400 mg/kg AZT or 200 mg/kg 3TC, pharmacokinetics were determined for AZT, AZT-5'-glucuronide, 3'-amino-3'-deoxythymidine (AMT), AZT-5'-phosphate, 3TC, and 3TC-5'-phosphate in serum of adult female mice [9].

Anatomical context of 3'-Aminothymidine

• Recently, we characterized the complete catabolic pathway of AZT in freshly isolated rat hepatocytes in suspension, demonstrating extensive formation of three catabolites, including GAZT, 3'-amino-3'-deoxythymidine (AMT), and 3'-amino-3'-deoxy-5'-beta-D-glucopyranuronosylthymidine (GAMT) [10].
• Penetration of 3'-amino-3'-deoxythymidine, a cytotoxic metabolite of zidovudine, into the cerebrospinal fluid of HIV-1-infected patients [11].

Associations of 3'-Aminothymidine with other chemical compounds

• The minor AZT metabolite, 3'-amino-3'-deoxythymidine (AMT), competitively inhibited thymidine transport with a Ki of 9.1 mM [12].

Gene context of 3'-Aminothymidine

• Further analysis demonstrated that the altered c-myb gene expression was largely due to the presence of 3'-amino-3'-deoxythymidine, a decomposition product of 3'-CNTU [13].
• These catabolites were identified as 3'-amino-3'-deoxythymidine (AMT) by fast atom bombardment mass spectrometry and 3'-amino-3'-deoxythymidine glucuronide (GAMT) through specific enzymatic hydrolysis [14].
• 3. 3'-amino-3'-deoxythymidine formation is probably mediated by both cytochrome P450 isozymes and NADPH-cytochrome P450 reductase [15].

Analytical, diagnostic and therapeutic context of 3'-Aminothymidine

• High-performance liquid chromatography analyses of the extracellular medium and cell extracts revealed the presence of unchanged dimer, AZT, 3'-azido-3'-deoxy-5'-beta-D-glucopyranosylthymidine (GAZT), 3'-amino-3'-deoxythymidine (AMT), ddI, and a previously unrecognized derivative of the dideoxyribose moiety of ddI, designated ddI-M [16].

References