A brief history of ABL-TKI's attempts across BBB...
[Quoted from multiple sources]
Imatinib - "The cerebrospinal fluid (CSF) concentration of imatinib is less than 3% that of plasma in patients."
"Nilotinib concentration in liver is approximately 9–11 fold higher than plasma but CNS exposure is limited with brain and spinal cord concentrations being only 6 and 5% of plasma levels."
"Dasatinib brain concentrations were, on average, 12- to 31-fold lower than in plasma (ie, brain/plasma ratio or brain penetrance of 3.2%-8.6%."
Bosutinb - "No radioactivity was detected in the brain, indicating that bosutinib did not pass the blood-brain barrier."
"Bafetinib (INNO-406) does not sufficiently cross intact or disrupted blood-brain barrier, and therefore, systemic administration of bafetinib is not recommended when investigating this drug as a treatment for brain tumours."
Sorafenib - "Blood/brain penetration was low as indicated by brain uptake less than 10 % of blood or plasma exposure."
"Ponatinib was 2.79 times greater in brain relative to blood on an area under the curve (AUC) basis and 2.26 times greater on a the basis of maximum concentration observed (Cmax). The observed elimination half-life was also longer in brain than in blood."
Let's tally the score...0-10% for all other TKI's versus 279% for Ponatinib. I think we have clear winner, and with what will surely be an exceptional safety profile at something like 20-30mg dose per day.
