Claturafenib ( PF-07799933) is an orally active inhibitor of pan-mutant BRAF. Claturafenib inhibits pERK in cells ( IC50 value of 1.6 nM in HT29 cells). Claturafenib has anticancer activity against BRAF G469A mutant NSCLC and BRAF K601E mutant melanoma [1].
In Vivo, Claturafenib (30 mg/kg; p.o.; once daily) causes tumor regressions in subcutaneous xenografts of CTG-1441 PDX, CTG-0362 PDX, and BxPC-3 in female Foxn1nu mice[1].
In Vitro, Claturafenib demonstrates broad inhibition of pERK levels in cell lines harboring Class I (IC50 = 0.7-7 nM), II (10-14 nmol/L), III (0.8-7.8 nM), and indel (113-179 nM) mutants, acquired BRAF p61 splice variant (59 nM), and acquired NRASQ61K (16 nM)[1].
References:
[1]. Rona Yaeger, et al. A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation. Cancer Discov. 2024 Sep 4;14(9):1599-1611.
In Vivo, Claturafenib (30 mg/kg; p.o.; once daily) causes tumor regressions in subcutaneous xenografts of CTG-1441 PDX, CTG-0362 PDX, and BxPC-3 in female Foxn1nu mice[1].
In Vitro, Claturafenib demonstrates broad inhibition of pERK levels in cell lines harboring Class I (IC50 = 0.7-7 nM), II (10-14 nmol/L), III (0.8-7.8 nM), and indel (113-179 nM) mutants, acquired BRAF p61 splice variant (59 nM), and acquired NRASQ61K (16 nM)[1].
References:
[1]. Rona Yaeger, et al. A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation. Cancer Discov. 2024 Sep 4;14(9):1599-1611.