Anti-cancer activity of a novel small molecule compound that simultaneously activates p53 and inhibits NF-κB signaling.

The p53 and NF-κB pathways play important roles in diverse cellular functions, including cell growth, apoptosis, and tumorigenesis. Mutations that inactivate the p53 gene and constitutive NF-κB pathway activation are common occurrences in human cancers. Although many drugs are being developed that selectively activate p53 or inhibit NF-κB, there are few drug candidates that can do both.

Small molecule-based disruption of the Axin/β-catenin protein complex regulates mesenchymal stem cell differentiation.

The Wnt/β-catenin pathway plays important roles in the differentiation of multiple cell types, including mesenchymal stem cells. Using a cell-based chemical screening assay with a synthetic chemical library of 270 000 compounds, we identified the compound SKL2001 as a novel agonist of the Wnt/β-catenin pathway and uncovered its molecular mechanism of action. SKL2001 upregulated β-catenin responsive transcription by increasing the intracellular β-catenin protein level and inhibited the phosphorylation of β-catenin at residues Ser33/37/Thr41 and Ser45, which would mark it for proteasomal degradation, without affecting CK1 and GSK-3β enzyme activities.

Synthesis and pharmacological evaluation of 3-aryl-3-azolylpropan-1-amines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.

A series of 3-aryl-3-azolylpropan-1-amines was prepared and screened for its capability of inhibiting monoamine reuptake. Analogs with nanomolar potency, good human in vitro microsomal stability, and low drug-drug interaction potential were described. In vivo models were used to evaluate the compound 19r for antidepressive, anxiolytic, and analgesic activity.

YKP1447, A Novel Potential Atypical Antipsychotic Agent.

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT(2A), Ki=0.61 nM, 5-HT(2C), Ki=20.7 nM) and dopamine (D(2), Ki=45.

Overexpression of Arabidopsis ACK1 alters leaf morphology and retards growth and development.

Cyclin dependent kinases (CDKs) play important roles in the plant cell cycle, a highly coordinated process in plant growth and development. To understand the regulatory network involving the CDKs, we have examined the role of ACK1, a gene that has significant homology to known ICKs (inhibitors of CDKs), but occupies a distinct branch of the ICK phylogenetic tree. Overexpression of ACK1 in transgenic Arabidopsis significantly inhibited growth, leading to effects such as serration of leaves, as a result of strong inhibition of cell division in the leaf meristem.

Cyclin D1 and p22ack1 play opposite roles in plant growth and development.

The plant cell division cycle, a highly coordinated process, is continually regulated during the growth and development of plants. In this report, we demonstrate how two cell-cycle regulators act together to control cell proliferation in transgenic Arabidopsis. To identify potential cyclin dependent kinase regulators from Arabidopsis, we employed an two-hybrid screening system to isolate genes encoding G1 specific cyclin-interacting proteins.

9-Hydroxypheophorbide alpha-induced apoptotic death of MCF-7 breast cancer cells is mediated by c-Jun N-terminal kinase activation.

Recently, we synthesized 9-hydroxypheophorbide alpha (9-HPbD), a new chlorophyll-derived photosensitizer. The photo-treatment of MCF-7 human breast cancer cells with 20 kJ/m2 of red light after 5 microM 9-HPbD pretreatment induced cell death, showed typical apoptotic features, i.e.