西亚试剂:PF-114, a potent and selective inhibitor of native and muta

PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome- positive (Ph ) leukemias harboring the T315I mutation.

A A Mian, A Rafiei, I Haberbosch, A Zeifman, I Titov, V Stroylov, A Metodieva, O Stroganov, F Novikov, B Brill, G Chilov, D Hoelzer, O G Ottmann, M Ruthardt.

Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance attributable to either kinase mutations in BCR/ABL or non-mutational mechanisms remains the major clinical challenge. With the exception of ponatinib, all approved TKIs are unable to inhibit the ‘gatekeeper’ mutation T315I. However, a broad spectrum of kinase inhibition increases the off target effects of TKIs and may be responsible for cardiovascular issues of ponatinib. Thus, there is a need for more selective options for the treatment of resistant Ph+ leukemias. PF-114 is a novel TKI developed with the specifications of i.) targeting T315I and other resistance mutations in BCR/ABL; ii.) achieving a high selectivity to improve safety; and iii.) overcoming non-mutational resistance in Ph+ leukemias.

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