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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The calicheamicins are a family of closely related antitumor antibiotics, with calicheamicin γ1 (Figure 5.57) the best known, produced by Micromonospora echinospora (ssp. Calichensis), a bacterium isolated from chalky soil or caliche clay, a type of soil found in Texas. The first example, calicheamicin γ1, was isolated in the mid-1980s from chalky soil in a “calichi pit” in Kerrville, Texas, collected by a scientist working for the pharmaceutical company Lederle Laboratories. Naming of the individual compounds is based on both thin-layer chromatography mobility using Greek letters with subscripts, and on the halogen substitution pattern that is indicted by the superscript. Calicheamicin γ1 and the related enediyne esperamicin are two of the most potent cytotoxic agents known.
Treatment and outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults after relapse
Published in Expert Review of Anticancer Therapy, 2020
Marie Balsat, Victoria Cacheux, Martin Carre, Emmanuelle Tavernier-Tardy, Xavier Thomas
CD22 is a 135-kDa sialoglycoprotein that mediates intercellular interactions for sialic-acid bearing ligands and modulates antigen receptor signaling and B-cell activation. CD22 is an important B cell-restricted surface antigen that is expressed in 96% of B cell-lineage ALL [103]. It is rapidly internalized on binding to anti-CD22 making it an attractive target for targeted therapy with chemotherapeutic conjugates. Following the development of gemtuzumab ozogamicin, an anti-CD33 antibody-drug conjugate, in acute myeloid leukemia, inotuzumab ozogamicin, an anti-CD22 antibody-drug conjugate, was developed. Inotuzumab ozogamicin is a humanized MoAb against CD22 conjugated via a bi-functional linker to a potent cytotoxic agent calicheamicin derived from Micromonospora echinospora, which induces DNA double-strand breaks and apoptosis independent of cell cycle progression [104]. Upon binding to CD22 receptors, inotuzumab is rapidly internalized, trafficked through lysosomes leading to hydrolysis of inactive calicheamicin. Calicheamicin is then reduced to its active form by intracellular glutathione. In the nucleus, active calicheamicin binds to DNA and generates free radicals leading to DNA double-strand breaks and cellular apoptosis (Figure 2).
Potential of rare actinomycetes in the production of metabolites against multiple oxidant agents
Published in Pharmaceutical Biology, 2018
Fatemeh Mohammadipanah, Mana Momenilandi
The superoxide radical as well as other reactive oxygen species (ROS) contribute to the oxidative damage to living organisms that are involved in many pathological processes such as inflammation, atherosclerosis, cancer, aging, and similar systematic diseases (Halliwell 1992; Cos et al. 1998). In the superoxide radical scavenging assay, the generation of radicals and NBT reduction (Figure 3), was significantly inhibited (32 ± 0.14%) only by the extracts of Saccharothrix ecbatanensis UTMC 537 and Micromonospora echinospora UTMC 2091, which exhibited 23 ± 0.35 scavenging activity.