Lorlatinib (PF-06463922, Pfizer Oncology, Groton, CT, USA) is an oral TKI that
targets both ALK and ROS1 with high affinity and good CNS penetration [91].
Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2. Potent MEK inhibitor.
Lorlatinib is the sole third-generation ALK inhibitor at this time; it is approved for
ALK-positive NSCLC patients who progressed on at least two ALK inhibitors with
one being crizotinib or who progressed on alectinib or ceritinib if either is used in
the frontline setting.
Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, highly selective inhibitor of MEK1/2, which is active in human tumor xenograft models and is well tolerated within the therapeutic exposure range in animals[1].
MEK1: 19 nM (IC50); MEK2: 47 nM (IC50)
[1] iverson c, larson g, lai c, et al. rdea119/bay 869766: a potent, selective, allosteric inhibitor of mek1/2 for the treatment of cancer. cancer research, 2009, 69(17): 6839-6847.
