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Preformulation of New Biological Entities
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Riccardo Torosantucci, Vasco Filipe, Jonathan Kingsbury, Atul Saluja, Yatin Gokarn
ADCs are mAbs that are covalently bound to cytotoxic chemicals via (semi)synthetic linkers. Such immune conjugates combine the antitumor potency of highly cytotoxic small-molecule drugs with the high selectivity and favorable pharmacokinetic profile of mAbs. The first ADC to gain FDA approval was gemtuzumab ozogamicin (Mylotarg®) in 2000. It is a recombinant, humanized anti-CD33 mAb covalently linked to the cytotoxic antitumor antibiotic calicheamicin for the treatment of patients with acute myeloid leukemia. Brentuximab vedotin (Adcetris®), approved in 2011, is an anti-CD30 chimeric mAb coupled through a protease-cleavable linker to the antimitotic agent monomethyl auristatin E and is approved to treat relapsed or refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma. Ado-trastuzumab emtansine (Kadcyla®), approved in 2013, is a humanized anti-human epidermal growth factor receptor 2 (anti-HER2) mAb covalently linked to the microtubule inhibitory drug DM1 (a derivative of maytansine) and is approved for the treatment of HER2-positive metastatic breast cancer. More than 30 additional ADCs have entered clinical development (all for oncological indications), and there are an additional 30 in clinical trials [37].
Iodine is needed to maintain health
Published in Tatsuo Kaiho, Iodine Made Simple, 2017
In 1981, calicheamicin was isolated from bacteria existing in caliches (limestone) in Kerrville, Texas. The cytotoxicity of calicheamicin is 3000 times stronger than general anticancer drugs, and was first marketed in 2000 as Gemtuzumab ozogamicin, a molecular target drug for nonsolid carcinoma acute myeloid leukemia. The carbohydrate chain in calicheamicin recognizes and bonds with the DNA (deoxyribonucleic acid) sequence, and the core of the enediyne generates biradicals which cause DNA cleavage. Currently, the iodine atoms are thought to determine positioning of the attack site.
Production of Life-Saving Drugs from Marine Sources
Published in Prasenjit Mondal, Ajay K. Dalai, Sustainable Utilization of Natural Resources, 2017
Doxorubicin (50), calicheamicin (51), auristatins, and maytansine (52) are important cytotoxic payloads conjugated with antibodies. Calicheamicin is a DNA-alkylating agent produced by Micromonospora echinospora ssp. calichensis. Gemtuzumab ozogamicin (Wyeth) is a representative example of a calicheamicin-based ADC. Another calicheamicin-based ADC, Inotuzumab ozogamicin (CMC-544, Pfizer) derived via linking an antibody anti-CD22 IgG4 monoclonal antibody is in phase III of clinical trials.
3,4-Dichloro-1,2,5-thiadiazole: a commercially available electrophilic sulfur transfer agent and safe resource of ethanedinitrile
Published in Journal of Sulfur Chemistry, 2022
Hayedeh Gorjian, Nader Ghaffari Khaligh
The symmetrical trisulfides were used in the pesticide and the rubber industry [11]. Dimethyl trisulfide (DMTS) application as a promising high-capacity catholyte for rechargeable lithium-ion batteries was demonstrated [12]. Furthermore, the anti-apoptotic effect of diallyl trisulfide (DATS) was studied on HG-exposed cardiac cells [13]. Synthetic organotrisulfides are stable in aqueous and biological systems, and their beneficial and harmful effects in biological systems have been reviewed [14]. Some of them have been exhibited cytotoxic properties [15], anticancer [16,17], and antibacterial [18] activities. Recently, it was reported that insertion of a trisulfide bond could cause high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity of doxorubicin homodimeric prodrugs [19]. Furthermore, the enediyne-containing trisulfides, including calicheamicin class and epipolythiodiketopiperazine alkaloids such as (+)-Luteoalbusin B have attracted significant attention for their antibiotic and antitumor activities. It is indicated that the allylic trisulfide moiety acts as a redox-activated trigger [20,21] (Figure 1).