Thermomechanical effect in a cylindrically-hybrid nematic liquid crystal

Thermomechanical rotation of a cylindrically-hybrid nematic liquid crystal in the presence of a longitudinal temperature gradient is predicted theoretically and detected experimentally. Pis’ma Zh. Tekh. Fiz. 25, 71–73 (March 26, 1999)     

Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.     

Thermomechanical effect in a hybrid-oriented nematic liquid crystal

The first experimental observation of a thermomechanical effect in a homeotropically planaroriented nematic liquid crystal is reported. The effect consists of the appearance of a hydrodynamic flow induced by a longitudinal temperature gradient. The measured value of the thermomechanical coefficient agrees well with the theoretical estimate. Pis’ma Zh. Tekh. Fiz. 23, 77–81 (September 12, 1997)     

Design,Synthesis and Anticancer Profile of New 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine-Linked Sulfonamide Derivatives with V600EBRAF Inhibitory Effect

A new series of 4-(1H-benzo[d]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives 12a–n was designed and synthesized according to the structure of well-established V600EBRAF inhibitors. The terminal sulfonamide moiety was linked to the pyrimidine ring via either ethylamine or propylamine bridge. The designed series was tested at fixed concentration (1 µM) against V600EBRAF, finding that 12e, 12i and 12l exhibited the strongest inhibitory activity among all target compounds and 12l had the lowest IC₅₀ of 0.49 µM. They were further screened on NCI 60 cancer cell lines to reveal that 12e showed the most significant growth inhibition against multiple cancer cell lines. Therefore, cell cycle analysis of 12e was conducted to investigate the effect on cell cycle progression. Finally, virtual docking studies was performed to gain insights for the plausible binding modes of vemurafenib, 12i, 12e and 12l.