Doxorubicin in the experimental study, doxorubicin, and Arcamone by DiMarco, a research team led by inducing a mutation in Streptomyces strains, obtained a new mutant, and made from the fermentation of a strain of sugar Xi antibiotics. Chemical structure and DNR (DNR) is similar, only 14 carbon atoms in the side chain for the porcelain base. 1968 animal experiments confirmed that doxorubicin has anti-tumor effect, the same year the first clinical trials Bonadonna.
Doxorubicin can be embedded in DNA between adjacent base pairs, so that DNA chain cleavage, impeding the synthesis of DNA and RNA. Doxorubicin in the experimental study, in addition, the drug under the action of the enzyme reduced to half-stuffed free radicals, react with oxygen can lead to the formation of oxygen free radicals, which may be related to cardiac toxicity. The destruction of the drug are still special role of cell membrane structure and function of both the benefits ring containing fat-soluble ligands, there are water-soluble glue soft brown sugar, and acidic and basic amino hope porcelain base, so it has a strong anti- cancer activity. Most sensitive to the S phase, M phase, followed by the less sensitive to the G1 phase of G1, S and G2 phase of a delayed effect.
Tumor cells to doxorubicin are mostly produced by multi-drug resistance tolerance, once produced MDR, may have other cross-resistance to many anticancer drugs.
Doxorubicin broad-spectrum anti-tumor. Tumor cells in vitro demonstrate that it has some selection. In vivo tests showed that doxorubicin for many animals transplanted tumors, such as breast cancer, leukemia, Yoshida sarcoma and P cut the anti-tumor effects than DNR strong.
Doxorubicin in the experimental study, intravenous doxorubicin, its plasma protein binding rate is very low, into the body rapidly distributed in the liver, spleen, lung, kidney and heart, but not through the blood brain barrier one. Doxorubicin clearance curve is heterogeneous, and its three-phase t1 / 2 were 0.5h, 3h and 40h or so. Metabolites mainly in the liver, primarily by biliary excretion, only 5% -10% in 6h urine excreted from within, can also occur in other organizations, the main metabolite of 50% to the prototype, with 23% of the activity of doxorubicin metabolites discharge of alcohol in the form of doxorubicin.