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Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program.

ABSTRACT: PF-03084014, a ?-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0?nM to 10??M) and against the in vivo xenograft panels (administered orally twice daily on Days 1-7 and 15-21). PF-03084014 demonstrated limited in vitro activity, with no cell line achieving ?50% inhibition. PF-03084014 induced significant differences in EFS distribution in 14 of 35 (40%) solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1 mutation), but objective responses were not observed. PF-03084014 demonstrated limited single agent activity in vitro and in vivo against the pediatric preclinical models studied.

SUBMITTER: Carol H 

PROVIDER: S-EPMC4225044 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program.

Carol Hernan H   Maris John M JM   Kang Min H MH   Reynolds C Patrick CP   Kolb E Anders EA   Gorlick Richard R   Keir Stephen T ST   Wu Jianrong J   Kurmasheva Raushan T RT   Houghton Peter J PJ   Smith Malcolm A MA   Lock Richard B RB   Lyalin Dmitry D  

Pediatric blood & cancer 20140324 8

PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0 nM to 10 μM) and against the in vivo xenograft panels (administered orally twice daily on Days 1-7 and 15-21). PF-03084014 demonstrated limited in vitro activity, with no cell line achieving ≥50% inhibition. PF-03084014 induced significant differences in EFS distribution in 14 of 35 (40%) solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1 mutation), but objective responses were n  ...[more]

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