Theranostic Rhenium Complexes as Suborganelle-Targeted Copper Ionophores To Stimulate Cuproptosis for Cancer Immunotherapy.

Being a recently identified mode of programmed cell demise, the functional implications of cuproptosis in the genesis, progression, and therapeutic modulation of cancer remain largely unknown. Given that cuproptosis is predominantly elicited by cellular copper overload, notably attributable to the dysregulation of copper homeostasis within mitochondria, we designed a series of phosphorescent rhenium(I) complexes (-) as suborganelle-targeted copper ionophores. Among them, can successfully transport extracellular copper into mitochondria and the Golgi apparatus and especially enrich copper into mitochondria.

IDO1 Inhibition Promotes Activation of Tumor-intrinsic STAT3 Pathway and Induces Adverse Tumor-protective Effects.

Pharmacological inhibition of IDO1 exhibits great promise as a strategy in cancer therapy. However, the failure of phase III clinical trials has raised the pressing need to understand the underlying reasons for this outcome. To gain comprehensive insights into the reasons behind the clinical failure of IDO1 inhibitors, it is essential to investigate the entire tumor microenvironment rather than focusing solely on individual cells or relying on knockout techniques.

Combination of apatinib with apo-IDO1 inhibitor for the treatment of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world. Recently, many clinical studies have demonstrated the therapeutic potential of immune checkpoint therapy combined with inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2) in colon cancer. Compound B37, identified in our previous experiment, is an apo-form indoleamine-2,3-dioxygenase 1 inhibitor (apo-IDO1 inhibitor), which has been shown to significantly suppress tumor growth combined with an anti-PD1 antibody.

Apo-Form Selective Inhibition of IDO for Tumor Immunotherapy.

The pharmacological inhibition of IDO1 is considered an effective therapeutic approach for cancer treatment. However, the inadequate response of existing holo-IDO1 inhibitors and unclear biomarkers available in clinical practice limit the possibility of developing efficacious IDO1 inhibitors. In the current study, we aimed to elucidate the activity and mechanism of a potent 1-pyrrole-2-carboxylic acid derivative (B37) targeting apo-IDO1 and to determine its role in tumor therapy.

Direct Syntheses of Nanocages and Frameworks Based on Anderson-Type Polyoxometalates via One-Pot Reactions.

A new one-step synthetic protocol of tris-functionalized Anderson polyoxomolybdates directly from heptamolybdate salts was presented in this Communication. Through this new method, we obtained the first example of Anderson-type polyoxomolybdates with vanadium as the heteroatom. Moreover, the crystals of the products exhibited interesting nanocage or framework extended structures, which were greatly affected by the trialkoxyl ligands as well as the counterions.