Disease relevance of Iododoxorubicin

• Pharmacology and clinical toxicity of 4'-iodo-4'-deoxydoxorubicin: an example of successful application of pharmacokinetics to dose escalation in phase I trials [1].
• New drug therapy of amyloidoses: resorption of AL-type deposits with 4'-iodo-4'-deoxydoxorubicin [2].
• Adoptive transfer of lymphokine-activated killer cells loaded with 4'-deoxy-4'-iododoxorubicin: therapeutic effect in mice bearing lung metastases [3].
• Characterization of tumor cell resistance to 4'-deoxy-4'-iododoxorubicin developed in Ehrlich ascites cells in vivo [4].
• In vivo, the spectrum of activity of 4'-iodo-4'-deoxydoxorubicin is comparable to that of DXR, but the new compound has higher activity against murine P388 leukemia resistant to DXR and against pulmonary metastases from Lewis lung carcinoma [5].

High impact information on Iododoxorubicin

• Interaction of the anthracycline 4'-iodo-4'-deoxydoxorubicin with amyloid fibrils: inhibition of amyloidogenesis [6].
• We studied the potential use of lymphokine-activated killer (LAK) cells loaded with 4'-deoxy-4'-iododoxorubicin (IDX) in adoptive immunotherapy experiments [3].
• CONCLUSIONS: Our results especially show that myelosuppression that is induced by 4'-iodo-4'-deoxydoxorubicin can be well predicted by the measure of the AUC of the drug and its metabolite [7].
• Blood cell counts after 4'-iodo-4'-deoxydoxorubicin treatment showed significant correlations among the surviving fractions of both granulocytes and platelets and the AUCs of the parent drug and its metabolite; the most significant correlations were obtained for the granulocytes and the metabolite [7].
• In vitro 4'-iodo-4'-deoxydoxorubicin is more cytotoxic than DXR against a panel of human and murine cell lines and is characterized by a higher and faster uptake [5].

Chemical compound and disease context of Iododoxorubicin

• A short-term antimetabolic assay based on the interference with 3H-thymidine and 3H-uridine incorporation after 3 hours of in vitro treatment was used to compare the cytotoxicity of a new halogenated anthracycline, 4'-Iodo-4'-deoxydoxorubicin (IDX), with that of its parent compound Doxorubicin (DX) against 44 human colorectal carcinomas [8].

Biological context of Iododoxorubicin

• Molecular structure of the halogenated anti-cancer drug iododoxorubicin complexed with d(TGTACA) and d(CGATCG) [9].
• Based on our previous Phase I study indicating good tolerability of the drug, we have evaluated therapeutic activity and acute and subacute toxicities associated with repeated courses of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-Dox) at the maximum tolerated dose (80 mg/m2) every three weeks [10].
• Effects of lipophilicity and protein binding on the hepatocellular uptake and hepatic disposition of two anthracyclines, doxorubicin and iododoxorubicin [11].
• In cardiac sarcosomes all the anthracyclines tested enhanced NADPH-dependent superoxide formation which followed Michaelis-Menten kinetics and their Vmax were similar to that of doxorubicin except 5-iminodaunorubicin which did not affect superoxide production and 4'-iodo-4'-deoxydoxorubicin which showed significantly lower Vmax and Km [12].

Anatomical context of Iododoxorubicin

• On the contrary, iododoxorubicin, FCE23762, and 4-demethoxy-daunorubicin accumulate to nearly the same extent into sensitive and resistant K562 cells [13].
• These offer limited benefit when cardiac involvement is significant, but newer treatments, including the novel anthracycline 4'-iodo-4'-deoxydoxorubicin, potentially combined with autologous stem cell transplantation, offer some hope for the future [14].

Associations of Iododoxorubicin with other chemical compounds

• For a set of five derivatives (doxorubicin, daunorubicin, 4-demethoxydaunorubicin, 4'-deoxy-4'-iododoxorubicin, and 13-dihydro-4'-deoxy-4'-iododoxorubicin), data were given on the rates of diffusional drug uptake, and membrane permeability coefficients of the noncharged molecules were estimated [15].
• Based on the proposed mechanism for TTR amyloid fibril formation we discuss the action of some of the proposed TTR stabilizers such as derivatives of some NSAIDs (diflunisal, diclofenac, flufenamic acid, and derivatives) and the action of amyloid disrupters such as 4'-iodo-4'-deoxydoxorubicin (I-DOX) and tetracyclines [16].

Gene context of Iododoxorubicin

• These compounds include dyes such as Congo Red, the antibiotic rifampicin, the anthracycline 4'-iodo-4'-deoxydoxorubicin, and a large variety of Abeta-derived peptides and modified peptides, among other reported inhibitors [17].
• 4'-Iodo-4'-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid [18].
• These data also suggest that the cytotoxicity of iododoxorubicin and 4-demethoxy-daunorubicin is related to the fact they are not transported by P-glycoprotein [19].
• The new anthracycline analogue, 4'-iodo-4'-deoxydoxorubicin (I-DOX), was administered at 70 mg/m2 as first chemotherapy in 61 patients with advanced NSCL (19), colon (20) and breast cancers (22) [20].
• We studied by transmission electron microscopy the effect of the drug 4'-iodo-4'-deoxydoxorubicin (I-DOX) on the in vitro assembly of TTR Leu55Pro fibrils by following fibril growth over a 15 day period [21].

Analytical, diagnostic and therapeutic context of Iododoxorubicin

• 4'-Deoxy-4'-iododoxorubicin, a halogenated anthracycline derivative, is an anticancer agent currently under Phase II clinical trials [9].
• Intracellular mapping of 4'-deoxy-4'-iododoxorubicin in sensitive and multidrug resistant cells by electron spectroscopic imaging [22].
• Studies of iododoxorubicin by HPLC [23].

References