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

doi:10.1002/pbc.23167

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

Producción científica: Article › revisión exhaustiva

75 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Páginas (desde-hasta)	636-639
Número de páginas	4
Publicación	Pediatric Blood and Cancer
Volumen	58
N.º	4
DOI	https://doi.org/10.1002/pbc.23167
Estado	Published - abr 2012
Publicado de forma externa	Sí

ASJC Scopus subject areas

Hematology
Oncology
Pediatrics, Perinatology, and Child Health

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10.1002/pbc.23167

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

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.",

keywords = "Developmental therapeutics, Preclinical testing, SMAC mimetic",

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

year = "2012",

month = apr,

doi = "10.1002/pbc.23167",

language = "English (US)",

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pages = "636--639",

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AU - Houghton, Peter J.

AU - Kang, Min H.

AU - Reynolds, C. Patrick

AU - Morton, Christopher L.

AU - Kolb, E. Anders

AU - Gorlick, Richard

AU - Keir, Stephen T.

AU - Carol, Hernan

AU - Lock, Richard

AU - Maris, John M.

AU - Billups, Catherine A.

AU - Smith, Malcolm A.

PY - 2012/4

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AB - 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.

KW - Developmental therapeutics

KW - Preclinical testing

KW - SMAC mimetic

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

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