Selective Degradation of GSPT1 by Cereblon Modulators Identified via a Focused Combinatorial Library was written by Powell, Chelsea E.;Du, Guangyan;Che, Jianwei;He, Zhixiang;Donovan, Katherine A.;Yue, Hong;Wang, Eric S.;Nowak, Radoslaw P.;Zhang, Tinghu;Fischer, Eric S.;Gray, Nathanael S.. And the article was included in ACS Chemical Biology in 2020.Computed Properties of C8H8Cl2N4 This article mentions the following:
Cereblon (CRBN) is an E3 ligase adapter protein that can be reprogrammed by imide-class compounds such as thalidomide, lenalidomide, and pomalidomide to induce the degradation of neo-substrate proteins. In order to identify addnl. small mol. CRBN modulators, we implemented a focused combinatorial library approach where we fused an imide-based CRBN-binding pharmacophore to a heterocyclic scaffold, which could be further elaborated. We screened the library for CRBN-dependent antiproliferative activity in the multiple myeloma cell line MM1.S and identified five hit compounds Quant. chem. proteomics of hit compounds revealed that they induced selective degradation of GSPT1, a translation termination factor that is currently being explored as a therapeutic target for the treatment of acute myeloid leukemia. Mol. docking studies with CRBN and GSPT1 followed by analog synthesis identified a possible hydrogen bond interaction with the central pyrimidine ring as a mol. determinant of hit compounds’ selectivity. This study demonstrates that a focused combinatorial library design, phenotypic screening, and chem. proteomics can provide a suitable workflow to efficiently identify novel CRBN modulators. In the experiment, the researchers used many compounds, for example, 2,6-Dichloro-9-isopropyl-9H-purine (cas: 203436-45-7Computed Properties of C8H8Cl2N4).
2,6-Dichloro-9-isopropyl-9H-purine (cas: 203436-45-7) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Computed Properties of C8H8Cl2N4
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics