CHMFL-KIT-64 is a potent and orally available inhibitor of wild-type c-KIT and a range of known c-KIT resistance mutants [1
]. It has demonstrated anti-tumour efficacy in vitro
, in mouse xenograft models, and against imatinib-resistant patient tumour cells expressing wild-type c-KIT. It has been proposed as a potential clinical lead for gastrointestinal stromal tumour (GIST) therapy as the majority (80-85%) of GISTs harbour c-KIT activation mutations. Other c-KIT mutations confer primary or secondary (acquired) resistance to imatinib
which is the first line drug used to combat GISTs. CHMFL-KIT-64 was designed to target mutations that are refractory to currently approved therapeutics including imatinib, sunitinib
. It can potently inhibit the T670I ATP binding pocket (gatekeeper) mutant that is resistant to many other c-KIT inhibitors.