These type I compounds are successful in the treatment of BRAFV600E-mutant melanoma, but are limited by their failure to inhibit wild-type RAF; rather, they induce dimerisation of wild RAF proteins by stabilising the dimer interface, leading to paradoxical activation of MEK1/2 and thence ERK1/2 through the uninhibited dimer partner [24]. The gene discussed is MAPK3; the disease is melanoma.