Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program

Peter J. Houghton, Min H. Kang, C. Patrick Reynolds, Christopher L. Morton, E. Anders Kolb, Richard Gorlick, Stephen T. Keir, Hernan Carol, Richard Lock, John M. Maris, Catherine A. Billups, Malcolm A. Smith

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0nM to 10.0μM) and the PPTP in vivo panels (30 or 75mg/kg [solid tumors] or 100mg/kg [ALL]) administered orally twice in a week. LCL161 showed a median relative IC 50 value of >10μM, being more potent against several leukemia and lymphoma lines. In vivo LCL161 induced significant differences in EFS distribution in approximately one-third of solid tumor xenografts (osteosarcoma and glioblastoma), but not in ALL xenografts. No objective tumor responses were observed. In vivo LCL161 demonstrated limited single agent activity against the pediatric preclinical models studied.

Original languageEnglish (US)
Pages (from-to)636-639
Number of pages4
JournalPediatric Blood and Cancer
Volume58
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Pediatrics
Heterografts
Osteosarcoma
Glioblastoma
Lymphoma
Neoplasms
Leukemia
LCL161
N-propyl-4-phenyl-1,2,3,6-tetrahydropyridine
In Vitro Techniques

Keywords

  • Developmental therapeutics
  • Preclinical testing
  • SMAC mimetic

ASJC Scopus subject areas

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

Cite this

Houghton, P. J., Kang, M. H., Reynolds, C. P., Morton, C. L., Kolb, E. A., Gorlick, R., ... Smith, M. A. (2012). Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program. Pediatric Blood and Cancer, 58(4), 636-639. https://doi.org/10.1002/pbc.23167

Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program. / Houghton, Peter J.; Kang, Min H.; Reynolds, C. Patrick; Morton, Christopher L.; Kolb, E. Anders; Gorlick, Richard; Keir, Stephen T.; Carol, Hernan; Lock, Richard; Maris, John M.; Billups, Catherine A.; Smith, Malcolm A.

In: Pediatric Blood and Cancer, Vol. 58, No. 4, 04.2012, p. 636-639.

Research output: Contribution to journalArticle

Houghton, PJ, Kang, MH, Reynolds, CP, Morton, CL, Kolb, EA, Gorlick, R, Keir, ST, Carol, H, Lock, R, Maris, JM, Billups, CA & Smith, MA 2012, 'Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program', Pediatric Blood and Cancer, vol. 58, no. 4, pp. 636-639. https://doi.org/10.1002/pbc.23167
Houghton, Peter J. ; Kang, Min H. ; Reynolds, C. Patrick ; Morton, Christopher L. ; Kolb, E. Anders ; Gorlick, Richard ; Keir, Stephen T. ; Carol, Hernan ; Lock, Richard ; Maris, John M. ; Billups, Catherine A. ; Smith, Malcolm A. / Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program. In: Pediatric Blood and Cancer. 2012 ; Vol. 58, No. 4. pp. 636-639.
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