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The Benoist 2014 study used the HGF/MET dimerization antagonist Hinge to block Dihexas procognitive activity in scopolamine-impaired rats, with oral Dihexa (2 mg/kg/day) reversing the scopolamine-induced Morris water maze deficit when administered alone but losing effect when co-administered with Hinge [3]

However, small-molecule 3 was quite lipophilic (logD 7.4 = 5.7), resulting in high metabolic intrinsic clearance in human liver microsomes (HLM) (CL int = 130 mL/min/kg, Table S4), which would likely lead to a short pharmacokinetic half-life (t 1/2 ) and the requirement for an unacceptably high daily dose in humans