RKIP Induction Promotes Tumor Differentiation via SOX2 Degradation in NF2-Deficient Conditions.

Unlabelled: Loss of NF2 (merlin) has been suggested as a genetic cause of neurofibromatosis type 2 and malignant peripheral nerve sheath tumor (MPNST). Previously, we demonstrated that NF2 sustained TGFβ receptor 2 (TβR2) expression and reduction or loss of NF2 activated non-canonical TGFβ signaling, which reduced Raf kinase inhibitor protein (RKIP) expression via TβR1 kinase activity. Here, we show that a selective RKIP inducer (novel chemical, Nf18001) inhibits tumor growth and promotes schwannoma cell differentiation into mature Schwann cells under NF2-deficient conditions.

Discovery and optimization of novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides as bifunctional antidiabetic agents stimulating both insulin secretion and glucose uptake.

A novel series of 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides was designed, synthesized and evaluated for their biological activities on glucose-stimulated insulin secretion (GSIS). The cytotoxicity of all 41 novel compounds was screened to assess their pharmacological safety in pancreatic β-cells. A two-step optimization process was carried out to establish the structure-activity relationship for this class and subsequently we identified the most active analogue 26.

SAR optimization studies on a novel series of 2-anilinopyrimidines as selective inhibitors against triple-negative breast cancer cell line MDA-MB-468.

Triple-negative breast cancers (TNBCs) account for approximately 15% of breast cancer cases and exhibit an aggressive clinical behavior. In this study, we designed and synthesized two series of 2-anilinopyrimidines based on the structure of our previously reported compound 1 that act as a selective inhibitor of the basal-like TNBC cell line MDA-MB-468. Through the fine-tuning of 1, cyclic and acyclic amines at 4-position of the pyrimidine core were turned out to be crucial for the selectivity.