Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Because of its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast, and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors.

Lurasidone is an antipsychotic drug clinically used for the treatment of schizophrenia and bipolar disorder. During a mechanism‐based forced degradation study of lurasidone, two novel degradation products were observed under free radical‐mediated oxidative (via AIBN) and solution photolytic conditions. The structures of the two novel degradants were identified through an approach combining HPLC, LC‐MSn (n = 1, 2), preparative HPLC purification and NMR spectroscopy. The degradant formed under the free radical‐mediated condition is an oxidative degradant with half of the piperazine ring cleaved to form two formamides; a mechanism is proposed for the formation of the novel N,N′‐diformyl degradant, which should be readily applicable to other drugs that contain a piperazine moiety that is widely present in drug molecules. The degradant observed under the solution photolytic condition is identified as the photo‐induced isomer of lurasidone with the benzisothiazole ring altered into a benzothiazole ring.

A series of porous aromatic framework material units were obtained by performing microwave-assisted Sonogashira reactions in water without inert gas protection.

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