KRAS is the most frequently mutated driver oncogene in human cancer, and KRAS mutations are commonly associated with poor prognosis and resistance to standard treatment. The ability to effectively target and block the function of mutated KRAS has remained elusive despite decades of research. Recent findings have demonstrated that directly targeting KRAS-G12C with electrophilic small molecules that covalently modify the mutated codon 12 cysteine is feasible. We have discovered a series of tetrahydropyridopyrimidines as irreversible covalent inhibitors of KRAS-G12C with in vivo activity. The PK/PD and efficacy of compound 13 will be highlighted.

Strong contact adhesion is an important requirement for durable, manufacturable solar cells. Advanced contacting technologies require new methods to measure adhesion. We describe a scratch test for measuring contact adhesion that involves scanning a weighted stylus across the cell while measuring the horizontal force FD required to dislodge the contacts. FD is characteristic of the adhesive bond but independent of the contact height, stylus weight and scan speed. We observe that contact peeling depends also on the tensile strength of the metal finger. The tests provide a valuable way to assess and optimize the adhesion of metal contacts.