RIOK2
is an atypical kinase implicated in multiple human cancers.
Although recent studies establish the role of RIOK2 in ribosome maturation
and cell cycle progression, its biological functions remain poorly
elucidated, hindering the potential to explore RIOK2 as a therapeutic
target. Here, we report the discovery of CQ211, the most
potent and selective RIOK2 inhibitor reported so far. CQ211 displays a high binding affinity (K
d = 6.1 nM) and shows excellent selectivity to RIOK2 in both enzymatic
and cellular studies. It also exhibits potent proliferation inhibition
activity against multiple cancer cell lines and demonstrates promising
in vivo efficacy in mouse xenograft models. The crystal structure
of RIOK2-CQ211 sheds light on the molecular mechanism
of inhibition and informs the subsequent optimization. The study provides
a cell-active chemical probe for verifying RIOK2 functions, which
may also serve as a leading molecule in the development of therapeutic
RIOK2 inhibitors.
Hypervalent iodine chemistry has arose as an important field in organic chemistry in the past decades. Hypervalent iodine compounds, with reactivities similarly to transition metals in many different types of transformations, have attracted broad interests in organic community due to their practical advantages in the mild conditions, low costs, environmental benign and low toxicity. Great progresses have been made in this field. Chiral hypervalent iodine reagents or precursors have also been developed and utilized in a variety of asymmetric reactions in a stoichiometric or catalytic way. Important advances have been witnessed in the field of chiral hypervalent iodine chemistry in recent years. However, great limitations still exist. In this review, we have made a summary of different types of chiral hypervalent iodine reagents and precursors according to the characteristics of these compounds and the timeline. It may be helpful for the researchers to better understand the development and limitations of chiral hypervalent iodine chemistry. Keywords chirality; chiral hypervalent iodine; chiral aryl iodide; asymmetric reaction; catalytic asymmetric synthesis
A highly efficient intramolecular asymmetric C-arylation of acyclic -ester amides is demonstrated. The CuI/chiral diamine ligand catazyled reaction, with t-BuOLi as the necessary base in MeCN, afforded 3,3’-disubstituted chiral oxindoles...
An
alkyne–isocyanide [3 + 2] cycloaddition followed
by a
Boulton–Katritzky rearrangement and a ring expansion is demonstrated.
Different from the typical Boulton-Katritzky rearrangement, which
forms five-membered ring products, the rearrangement-ring expansion
method provides a mild, efficient, and atom-economical access to fused
9-deazaguanine structures in high yields.
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