molecules of the month

BAY 1895344 is a potent and highly selective inhibitor of the ATR kinase, which is involved in the DNA damage response. Further disruption of the DNA damage response via ATR inhibition is expected to induce synthetic lethality in cancers with already impaired DNA damage repair mechanisms. The Bayer team was able to overcome poor solubility in an initial lead to identify a highly orally bioavailable molecule. The acceptable solubility of 344 despite multiple aromatic rings is believed to be due to the out-of-plane bias of the methylpyrazole motif relative to the naphthyridine ring.