Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo.

The SAR and improvement in potency against Tie2 of novel thienopyrimidine and thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one of these compounds bound to the Tie-2 kinase domain is consistent with the SAR. These compounds have moderate potency in cellular assays of Tie-2 inhibition, good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.

Extracellular proteases produced by the Quorn® myco-protein fungus Fusarium graminearum in batch and chemostat culture.

was grown in batch and continuous (chemostat) culture on a glucose-mineral salts medium in the presence and absence of casein. In the absence of casein no protease activity was detected in the culture filtrate from either batch or chemostat culture. For batch cultures grown on medium containing casein, most of the proteolytic activity detected in the supernatant during exponential growth had an optimum at ca pH 5.