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

Hernan Carol; John M. Maris; Min H. Kang; C. Patrick Reynolds; E. Anders Kolb; Richard Gorlick; Stephen T. Keir; Jianrong Wu; Raushan T. Kurmasheva; Peter J. Houghton; Malcolm A. Smith; Richard B. Lock

doi:10.1002/pbc.25026

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

Hernan Carol, John M. Maris, Min H. Kang, C. Patrick Reynolds, E. Anders Kolb, Richard Gorlick, Stephen T. Keir, Jianrong Wu, Raushan T. Kurmasheva, Peter J. Houghton, Malcolm A. Smith, Richard B. Lock

Internal Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0nM to 10μM) 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.

Original language	English
Pages (from-to)	1493-1496
Number of pages	4
Journal	Pediatric Blood and Cancer
Volume	61
Issue number	8
DOIs	https://doi.org/10.1002/pbc.25026
State	Published - Aug 2014

Keywords

Developmental therapeutics
Notch inhibitors
Preclinical testing

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.25026

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

abstract = "PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0nM to 10μM) 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.",

keywords = "Developmental therapeutics, Notch inhibitors, Preclinical testing",

author = "Hernan Carol and Maris, {John M.} and Kang, {Min H.} and Reynolds, {C. Patrick} and Kolb, {E. Anders} and Richard Gorlick and Keir, {Stephen T.} and Jianrong Wu and Kurmasheva, {Raushan T.} and Houghton, {Peter J.} and Smith, {Malcolm A.} and Lock, {Richard B.}",

year = "2014",

month = aug,

doi = "10.1002/pbc.25026",

language = "English",

volume = "61",

pages = "1493--1496",

number = "8",

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T1 - Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program

AU - Carol, Hernan

AU - Maris, John M.

AU - Kang, Min H.

AU - Reynolds, C. Patrick

AU - Kolb, E. Anders

AU - Gorlick, Richard

AU - Keir, Stephen T.

AU - Wu, Jianrong

AU - Kurmasheva, Raushan T.

AU - Houghton, Peter J.

AU - Smith, Malcolm A.

AU - Lock, Richard B.

PY - 2014/8

Y1 - 2014/8

N2 - PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0nM to 10μM) 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.

AB - PF-03084014, a γ-secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0nM to 10μM) 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.

KW - Developmental therapeutics

KW - Notch inhibitors

KW - Preclinical testing

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SN - 1545-5009

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SP - 1493

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JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

IS - 8

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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