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 journalArticle

5 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1493-1496
Number of pages4
JournalPediatric Blood and Cancer
Volume61
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Heterografts
Pediatrics
Cell Line
Amyloid Precursor Protein Secretases
Mutation
2-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-3-ylamino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide
In Vitro Techniques
Neoplasms

Keywords

  • Developmental therapeutics
  • Notch inhibitors
  • Preclinical testing

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Carol, H., Maris, J. M., Kang, M. H., Reynolds, C. P., Kolb, E. A., Gorlick, R., ... Lock, R. B. (2014). Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program. Pediatric Blood and Cancer, 61(8), 1493-1496. https://doi.org/10.1002/pbc.25026

Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program. / Carol, Hernan; Maris, John M.; Kang, Min H.; Reynolds, C. Patrick; Kolb, E. Anders; Gorlick, Richard; Keir, Stephen T.; Wu, Jianrong; Kurmasheva, Raushan T.; Houghton, Peter J.; Smith, Malcolm A.; Lock, Richard B.

In: Pediatric Blood and Cancer, Vol. 61, No. 8, 2014, p. 1493-1496.

Research output: Contribution to journalArticle

Carol, H, Maris, JM, Kang, MH, Reynolds, CP, Kolb, EA, Gorlick, R, Keir, ST, Wu, J, Kurmasheva, RT, Houghton, PJ, Smith, MA & Lock, RB 2014, 'Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program', Pediatric Blood and Cancer, vol. 61, no. 8, pp. 1493-1496. https://doi.org/10.1002/pbc.25026
Carol, Hernan ; Maris, John M. ; Kang, Min H. ; Reynolds, C. Patrick ; Kolb, E. Anders ; Gorlick, Richard ; Keir, Stephen T. ; Wu, Jianrong ; Kurmasheva, Raushan T. ; Houghton, Peter J. ; Smith, Malcolm A. ; Lock, Richard B. / Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric preclinical testing program. In: Pediatric Blood and Cancer. 2014 ; Vol. 61, No. 8. pp. 1493-1496.
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