The discovery and development of Eg5 inhibitors for the clinic

The mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP, Kif11, a member of the kinesin-5 family) represents an attractive oncology drug target in the ongoing development of anti-mitotic drugs that selectively block mitosis through disruption to the mitotic spindle. In this state-of-the-art review, we outline the progress that has been made in the development of Eg5 inhibitors for clinical use. We evaluate the preclinical development and attributes of key Eg5 inhibitors that have undergone clinical evaluation or extensive preclinical optimisation, and discuss the medicinal chemistry strategies utilised in their design to overcome the challenges encountered during lead optimisation. We critically analyse the progress that has been made towards delivering clinical benefits, and the wider implications this has in the utility of mitotic kinesin inhibitors as prospective oncology drugs

Species diversification – which species should we use?

Large detector systems for particle and astroparticle physics; Particle tracking detectors; Gaseous detectors; Calorimeters; Cherenkov detectors; Particle identification methods; Photon detectors for UV. visible and IR photons; Detector alignment and calibration methods; Detector cooling and thermo-stabilization; Detector design and construction technologies and materials. The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems. as established by test beam measurements and simulation studies. is described. © 2008 IOP Publishing Ltd and SISSA