Identification of Novel Mutant (R132H) Isocitrate Dehydrogenase 1 Inhibitors for Glioma Therapy was written by Murali, Poornimaa;Karuppasamy, Ramanathan. And the article was included in Journal of Computational Biophysics and Chemistry in 2022.Name: 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid The following contents are mentioned in the article:
Neomorphic transformations in isocitrate dehydrogenase 1 (IDH1) are the key mutations prevalently found in various cancers including glioma. Recently identified mIDH1 specific inhibitors showed modest brain penetrating potential and dose-limiting toxicity. Herein, we elucidate virtual screening strategies to discover persuasive mIDH1 inhibitors from the approved subset of the DrugBank database consisting of 2715 mols. Initially, a structural similarity search identified a total of 1432 lead mols. The resultant compounds were inspected by mol. docking along with MM-GBSA and ADMET analyses. Altogether, the analyses identified Abemaciclib as the hit against mIDH1. Notably, abemaciclib was able to form hydrogen bond interaction with active site residues of mIDH1 protein. In the end, the dynamic behavior of the hit complex was also examined using mol. dynamics simulation studies. The outcome of the study culminates that the hit complex was stable throughout the simulation period of 100ns. It is worth noting that benzimidazole moiety of abemaciclib was reported to show inhibitory activity against glioma cells. Overall, these findings highlight that abemaciclib has the potential as a lead mol. against glioma. Indeed, the screened hit compound could be further explored for the development of mIDH1 inhibitor with great brain penetrating ability and low toxicity. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7Name: 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid).
4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Name: 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem