Singh, Rajeeva published the artcileAntibody-Drug Conjugates with Indolinobenzodiazepine Dimer Payloads: DNA-Binding Mechanism of Indolinobenzodiazepine Dimer Catabolites in Target Cancer Cells, Product Details of C18H34N4O5S, the publication is Molecular Pharmaceutics (2020), 17(1), 50-58, database is CAplus and MEDLINE.
DNA-targeting indolinobenzodiazepine dimer (IGN) payloads are used in several clin.-stage antibody-drug conjugates. IGN drugs alkylate DNA through the single imine moiety present in the dimer in contrast to the pyrrolobenzodiazepine dimer drugs, such as talirine and tesirine, which contain two imine moieties per dimer and cross-link DNA. This study explored the mechanism of binding of IGN to DNA in cells and to synthetic duplex and hairpin oligonucleotides. New, highly sensitive IGN-DNA binding ELISA methods were developed using biotinylated IGN analogs (monoimine, diimine, and diamine IGNs) and digoxigenin-labeled duplex oligonucleotides, which allowed the measurement of drug-DNA adducts in viable cells at concentrations below IC50. Furthermore, the release of free drug from the IGN-DNA adduct upon treatment with nuclease ex vivo was tested under physiol. conditions. The monoimine IGN drug formed a highly stable adduct with DNA in cells, with stability similar to that of the diimine drug analog. Both monoimine and diimine IGN-DNA adducts released free drugs upon DNA cleavage by nuclease at 37°C, although more free drug was released from the monoimine compared to the diimine adduct, which presumably was partly cross-linked. The strong binding of the monoimine IGN drug to duplex DNA results from both the noncovalent IGN-DNA interaction and the covalent bond formation between the 2-amino group of a guanine residue and the imine moiety in IGN.
Molecular Pharmaceutics published new progress about 359860-27-8. 359860-27-8 belongs to imidazoles-derivatives, auxiliary class Other Aliphatic Heterocyclic,Chiral,Amine,Amide,Ether,Inhibitor, name is N-(2-(2-(2-(2-Aminoethoxy)ethoxy)ethoxy)ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide, and the molecular formula is C12H16N2O2, Product Details of C18H34N4O5S.
Referemce:
https://en.wikipedia.org/wiki/Imidazole,
Imidazole | C3H4N2 – PubChem