Bruton’s tyrosine kinase (BTK) is an attractive therapeutic target in the treatment of cancer, inflammation, and autoimmune diseases. Covalent and noncovalent BTK inhibitors have been developed, among which covalent BTK inhibitors have shown great clinical efficacy. However, some of them could produce adverse effects, such as diarrhea, rash, and platelet dysfunction, which are associated with the off-target inhibition of ITK and EGFR. In this study, we disclosed a series of pteridine-7­(8H)-one derivatives as potent and selective covalent BTK inhibitors, which were optimized from 3z, an EGFR inhibitor previously reported by our group. Among them, compound 24a exhibited great BTK inhibition activity (IC50 = 4.0 nM) and high selectivity in both enzymatic (ITK >250-fold, EGFR >2500-fold) and cellular levels (ITK >227-fold, EGFR 27-fold). In U-937 xenograft models, 24a significantly inhibited tumor growth (TGI = 57.85%) at a 50 mg/kg dosage. Accordingly, 24a is a new BTK inhibitor worthy of further development.

In this paper, we propose a Social Vehicle Navigation system that integrates driver-provided information into a vehicle navigation system in order to calculate personalized routing. Our approach allows drivers registered into certain vehicle social network groups to share driving experiences with other drivers using voice tweets. These tweets are automatically aggregated into tweet digests for each social group based on location and destination. While listening to the tweet digests, a driver can instruct the social navigator to avoid or choose certain road segments in order to calculate a personalized route. We present our initial design along with a simple prototype implemented for the Android platform.

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