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

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 (US)
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
Externally published	Yes

Keywords

Developmental therapeutics
Notch inhibitors
Preclinical testing

ASJC Scopus subject areas

Hematology
Oncology
Pediatrics, Perinatology, and Child Health

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10.1002/pbc.25026

Cite this

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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 (US)",

volume = "61",

pages = "1493--1496",

journal = "Pediatric Blood and Cancer",

issn = "1545-5009",

publisher = "Wiley-Liss Inc.",

number = "8",

}

TY - JOUR

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

UR - https://www.scopus.com/pages/publications/84901984072

UR - https://www.scopus.com/pages/publications/84901984072#tab=citedBy

U2 - 10.1002/pbc.25026

DO - 10.1002/pbc.25026

M3 - Article

C2 - 24664981

AN - SCOPUS:84901984072

SN - 1545-5009

VL - 61

SP - 1493

EP - 1496

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

Access to Document

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