B13 Selectively Targeting Lung Cancer with a Novel Small Molecule that Induces Lethality Through Dual Inhibition of Disulfide Reductases

Identification from a combinatorial library of a small molecule that selectively induces apoptosis in cancer cells.

The selective induction of death in cancer cells is a major challenge in modern medicine. In this communication we describe the synthesis of an 88-membered combinatorial library, and the subsequent evaluation of these compounds for their ability to selectively induce apoptosis in cancerous cells. A compound was identified from the library that induces apoptosis in U-937 and HL-60 cell lines. Th...

A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer

Various carcinogens induce EGFR/RAS/MAPK signaling, which is critical in the development of lung cancer. In particular, constitutive activation of extracellular signal-regulated kinase 2 (ERK2) is observed in many lung cancer patients, and therefore developing compounds capable of targeting ERK2 in lung carcinogenesis could be beneficial. We examined the therapeutic effect of catechol in lung c...

Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer.

Chemotherapies that target thymidylate synthase (TS) continue to see considerable clinical expansion in non-small cell lung cancer (NSCLC). One drawback to TS-targeted therapies is drug resistance and subsequent treatment failure. Novel therapeutic and biomarker-driven strategies are urgently needed. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is reported to protect tumor...

Therapeutic Discovery Inhibition of dUTPase Induces Synthetic Lethality with Thymidylate Synthase–Targeted Therapies in Non–Small Cell Lung Cancer

Chemotherapies that target thymidylate synthase (TS) continue to see considerable clinical expansion in non–small cell lung cancer (NSCLC).Onedrawback to TS-targeted therapies is drug resistance and subsequent treatment failure. Novel therapeutic and biomarker-driven strategies are urgently needed. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is reported to protect tumor c...

A Novel Small-molecule Inhibitor Targeting