Some targeted agents implicated in the treatment of cancers, and their brain distribution

Targeted AgentPrimary IndicationPrimary TargetSubstrate StatusBrain-to-Plasma Ratio (Kp), MiceReference
VemurafenibaMelanomaMutant BRAFYesYes0.01Durmus et al. (2012), Mittapalli et al. (2012)
DabrafenibbMelanomaMutant BRAFYesYes0.04Mittapalli et al. (2013)
TrametinibcMelanomaMEKYesNo0.15 0.15 (Kp,uu)Vaidhyanathan et al. (2014)
Gampa et al. (2018)
CobimetinibdMelanomaMEKYesNo0.32 0.027 (Kp,uu)Choo et al. (2014)
OmipalisibaMelanomaPI3k/mTORYesYes0.06Vaidhyanathan et al. (2016)
PalbociclibBreast cancerCDK4/6YesYes0.2a 0.01 (Kp,uu)ede Gooijer et al. (2015), Parrish et al. (2015)
AbemaciclibeBreast cancerCDK4/6YesYes1.2 0.17 (Kp,uu)eRaub et al. (2015)
ImatinibfLeukemiaBCR-Abl TKYesYes0.2Soo et al. (2010)
SorafenibcHepatocellular and renal carcinomaCRAF, BRAF,KIT, FLT-3, VEGFRYesYes0.06Agarwal et al. (2011)
ErlotinibgNSCLCEGFRYesYes0.06 0.13 (Kp,uu)Kim et al. (2019a)
SunitinibhRenal carcinomaRTKYesYes2.3Chee et al. (2016)
GefitinibgNSCLCEGFRYesYes0.36 (Kp,uu) 0.1 (Kp,uu)iKim et al. (2019a)
LapatinibaBreast cancerEGFR/HER2YesYes0.03Polli et al. (2009)
DasatinibaLeukemiaBCR-Abl TKYesYes<0.12Chen et al. (2009)
NilotinibjLeukemiaBCR-Abl KYesYes0.002Lee et al. (2018)
  • AUC, area under the curve; BCRP, breast cancer resistance protein; EGFR, epidermal growth factor receptor; Kp, Brain-to-plasma ratio of the total concentrations; Kp,uu, brain-to-plasma ratio of the unbound concentrations; MEK, mitogen-activated protein kinase enzyme; NSCLC, non–small cell lung cancer; P-gp, P-glycoprotein; RTK, rhabdoid tumor of the kidney; VEGFR, vascular endothelial growth factor receptor.

  • a Steady-state brain-to-plasma concentration ratios.

  • b Brain-to-plasma ratio of AUC0–4 h after oral dose.

  • c Brain-to-plasma ratio of AUC0–tlast after intravenous dose.

  • d Brain-to-plasma ratio of concentrations 6 hours after oral dose.

  • e Brain-to-plasma ratios of concentrations 5 minutes after intravenous dose.

  • f Brain-to-plasma ratios of concentrations Cmax after oral dose.

  • g Brain-to-plasma ratio of AUC0–tlast after subcutaneous dose.

  • h Brain-to-plasma ratio of AUC0–∞ after oral dose.

  • j Brain-to-plasma ratio of AUC0–24 h after oral dose.