CFT1946 from C4 Therapeutics is a potent, selective, and orally bioavailable bifunctional degrader of mutant BRAF in Ph. I/II for the treatment of BRAF-driven solid tumors, alone and in combo with a MEK1/2 inhibitor (trametinib) (NCT05668585). BRAF-V600X is clinically validated with approved drugs (e.g. vemurafenib), but traditional inhibitors face challenges in selectivity over wildtype BRAF and can cause paradoxical RAF activation.