Compound 9 [PMID: 26006010] is a reversible BTK inhibitor that was designed to have a long target residency time with a resulting increase in the duration of in vivo
target engagement, and with the overall aim of improving in vivo
drug efficacy [1
]. Compound 9 has a cysteine-reactive, inverted cyanoacrylamide scaffold structure that interacts with Cys481, a residue that lies outwith the catalytic domain of the enzyme but close to the ATP pocket (and is also a target of the irreversible inhibitor ibrutinib
). It has good aqueous solubility and is orally bioavailable. Compound 9 may be PRN473 as described in [3
], but PRN473's structure has not been formally disclosed.