37904-72-6Relevant articles and documents
Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL
Yang, Lixin,Liu, Yongqing,Fan, Minghua,Zhu, Guiwang,Jin, Hongwei,Liang, Jing,Liu, Zhenming,Huang, Zhuo,Zhang, Liangren
, (2019/09/07)
Chemical probes of epigenetic ‘readers’ of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in physiology and pathology. However, only limited ‘reader’ probes have been developed, which restricted our understanding towards these macromolecules and their roles in cells or animals. Here, we reported a structure-guided approach to develop and characterize benzo [d]oxazol-2(3H)-one analogs as the first potent and selective small-molecule inhibitors of chromodomain Y-like (CDYL), a histone methyllysine reader protein. The binding conformation between the chromodomain of CDYL and the modified peptidomimetics was studied via molecular docking and dynamic simulations, facilitating subsequent virtual screening of tens of hits from Specs chemical library validated by SPR technique (KD values: from 271.1 μM to 5.4 μM). Further design and synthesis of 43 compounds helped to interpret the structure-activity relationship (SAR) that lead to the discovery of novel small-molecule inhibitors of CDYL. Compound D03 (KD: 0.5 μM) was discovered and showed excellent selectivity among other chromodomain proteins, including CDYL2 (>140 folds), CDY1 (no observed binding) and CBX7 (>32 folds). Moreover, we demonstrated that D03 engaged with endogenous CDYL in a dose-dependent manner, and perturbed the recruitment of CDYL onto chromatin, resulting in transcriptional derepression of its target genes. Finally, the results showed that D03 promoted the development and branching of neurodendrites by inhibiting CDYL in hippocampal and cortical cultured neurons. This study not only discovers the first selective small-molecule inhibitors of CDYL, but provids a new chemical tool to intervene the dynamic nature of bio-macromolecules involved in epigenetic mechanism.
Radiosynthesis of SPECT tracers: Via a copper mediated 123I iodination of (hetero)aryl boron reagents
Wilson, Thomas C.,McSweeney, Greg,Preshlock, Sean,Verhoog, Stefan,Tredwell, Matthew,Cailly, Thomas,Gouverneur, Véronique
supporting information, p. 13277 - 13280 (2016/11/17)
A general method for the copper mediated nucleophilic 123I-iodination of (hetero)aryl boronic esters and acids has been developed. The broad substrate scope of this radiosynthetic approach allows access to [123I]DPA-713, [123I]IMPY, [123I]MIBG and [123I]IPEB that are four commonly used SPECT radiotracers. Our results infer that aryl boronic reagents can now be employed as common precursors for both fluorine-18 and iodine-123 radiolabelling.
INHIBITORS OF HISTONE DEACETYLASE
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Paragraph 0272, (2016/04/26)
This invention provides compounds that are inhibitors of HDAC2. The compounds (e.g., compounds according to Formula (I), (II), (IIa), (III), (IV), (V), or (VI)) accordingly are useful for treating, alleviating, or preventing a condition in a subject such as a neurological disorder, memory or cognitive function disorder or impairment, extinction learning disorder, fungal disease or infection, inflammatory disease, hematological disease, or neoplastic disease, or for improving memory or treating, alleviating, or preventing memory loss or impairment.
