An article Analyzing Resistance to Design Selective Chemical Inhibitors for AAA Proteins WOS:000486630100009 published article about KINASE INHIBITORS; STRUCTURAL BASIS; ATPASE; P97; CANCER; MECHANISMS; UBIQUITIN; VCP/P97; SPASTIN; POTENT in [Pisa, Rudolf; Cupido, Tommaso; Steinman, Jonathan B.; Jones, Natalie H.; Kapoor, Tarun M.] Rockefeller Univ, Lab Chem & Cell Biol, New York, NY 10065 USA; [Pisa, Rudolf; Jones, Natalie H.] Rockefeller Univ, Triinst PhD Program Chem Biol, New York, NY 10065 USA; [Steinman, Jonathan B.] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY 10065 USA in 2019.0, Cited 45.0. Application In Synthesis of 1H-1,2,4-Triazol-5-amine. The Name is 1H-1,2,4-Triazol-5-amine. Through research, I have a further understanding and discovery of 61-82-5
Drug-like inhibitors are often designed by mimicking cofactor or substrate interactions with enzymes. However, as active sites are comprised of conserved residues, it is difficult to identify the critical interactions needed to design selective inhibitors. We are developing an approach, named RADD (resistance analysis during design), which involves engineering point mutations in the target to generate active alleles and testing compounds against them. Mutations that alter compound potency identify residues that make key interactions with the inhibitor and predict target-binding poses. Here, we apply this approach to analyze how diaminotriazole-based inhibitors bind spastin, a microtubule-severing AAA (ATPase associated with diverse cellular activities) protein. The distinct binding poses predicted for two similar inhibitors were confirmed by a series of X-ray structures. Importantly, our approach not only reveals how selective inhibition of the target can be achieved but also identifies resistance-conferring mutations at the early stages of the design process.
Application In Synthesis of 1H-1,2,4-Triazol-5-amine. About 1H-1,2,4-Triazol-5-amine, If you have any questions, you can contact Pisa, R; Cupido, T; Steinman, JB; Jones, NH; Kapoor, TM or concate me.
Reference:
Article; Safari, Niloufar; Shirini, Farhad; Tajik, Hassan; Journal of Molecular Structure; vol. 1201; (2020);,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics