molecules of the month

“compound Ia”

oral BRAF inhibitor, brain penetrant

effective in A375-derived mouse models

from prior paradox inducing BRAF inhibitors

Clinical Cancer Research


Chemical structure of molecule compound Ia Roche BRAF inhibitor
1 min read

6.     The Roche BRAF inhibitor, compound Ia, is designed to address the limitations of existing BRAFi/MEKi inhibitor combinations. It is a RAF paradox breaker (see belvarafenib) and is brain penetrant, offering the potential to address several mechanisms of resistance to approved agents and potentially reducing the need for MEKi combination (which brings in additional side effects). Preclinical superiority was demonstrated over approved BRAFi in macro-metastatic and disseminated micro-metastatic brain tumor models. The high CNS permeability could extend the duration of response in melanoma patients for whom brain metastases are a fatal and frequent outcome. Compound Ia was well-tolerated in mice at all doses tested (up to 180 mg/kg). CNS drug hunter Jake Schwarz says, “Limiting HBDs is a key component of brain penetration, and…

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