Description

Another member of the series of orally available pan-RAF/SFK inhibitor is active against treatment-naive BRAF and NRAS mutant tumors.  It is active in tumors from patients who developed resistance to BRAF-selective inhibitors and a BRAF plus MEK inhibitor combination.  This compound series could provide a first-line therapy for treatment naïve patients and a second-line therapy for a range of patients with relapsed melanoma.  Phase 1 clinical trials will commence in 2015 with this series of compounds.  IC50 0.03μM  and 0.01μM for BRAF kinase and SRC kinase respectively.

Systematic Name: 1-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl)-3-(2-(methylthio)-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)phenyl)urea

SMILES: CC(C)(C)C1=NN(C2=CC=CC=C2)C(NC(NC(C(SC)=C3)=CC=C3OC4=C5C(NC(C=N5)=O)=NC=C4)=O)=C1

Molecular Weight: 541.63

PubMed Ref.: 25500121

References

Girotti, Maria Romina, et al. "Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma." Cancer cell 27.1 (2015): 85-96.

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