Dissection of Targeting Molecular Mechanisms of Celastrol-induced Nephrotoxicity A Combined Deconvolution Strategy of Chemoproteomics and Metabolomics.

Celastrol (Cel), derived from the traditional herb fordii Hook. f., has anti-inflammatory, anti-tumor, and immunoregulatory activities.

Chemoproteomics Reveals Glaucocalyxin A Induces Mitochondria-Dependent Apoptosis of Leukemia Cells via Covalently Binding to VDAC1.

Chronic myelogenous leukemia (CML) that is resistant to tyrosine kinase inhibitors is one of the deadliest hematologic malignancies, and the T315I mutation in the breakpoint cluster region-Abelson (BCR-ABL) kinase domain is the most prominent point mutation responsible for imatinib resistance in CML. Glaucocalyxin A (GLA), a natural bioactive product derived from the Rabdosia rubescens plant, has strong anticancer activity. In this study, the effect and molecular mechanism of GLA on imatinib-sensitive and imatinib-resistant CML cells harboring T315I mutation via a combined deconvolution strategy of chemoproteomics and label-free proteomics is investigated.

A novel tubulin inhibitor, 6h, suppresses tumor-associated angiogenesis and shows potent antitumor activity against non-small cell lung cancers.

Tumor angiogenesis is closely associated with the metastasis and progression of non-small cell lung cancer (NSCLC), a highly vascularized solid tumor. However, novel therapeutics are lacking for the treatment of this cancer. Here, we developed a series of 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazol analogs (6a-6x) as tubulin colchicine-binding site inhibitors, aiming to find a novel promising drug candidate for NSCLC treatment.

The anti-MDR efficacy of YAN against A549/Taxol cells is associated with its inhibition on glycolysis and is further enhanced by 2-deoxy-d-glucose.

Aerobic glycolysis is a hallmark of malignant tumor. Here, the hyperactive glycolysis in multidrug-resistant A549/Taxol cells was demonstrated to be essential for maintaining the vigorous cell viability and drug resistance. 5-(4-ethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-3-amine (YAN), a newly synthesized tubulin inhibitor, could not only inhibit the glycolysis in A549 and A549/Taxol cells through down-regulating the glycolysis-related proteins, but also disrupt the mitochondrial localization of hexokinase-2 (HK-2) which is related with the apoptosis resistance.