title: Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program.
abstract: The PIM kinase inhibitor, SGI-1776, was tested against the PPTP in vitro (1.0 nM-10 µM) and in vivo panels (148 mg/kg daily × 5 days for 3 weeks). SGI-1776 exhibited cytotoxic activity in vitro with a median relative IC(50) of 3.1 µM. SGI-1776 induced significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts. SGI-1776 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induced complete responses of subcutaneous MV4;11 (B myeloid leukemia).
authors: Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.
authors: Vandana
authors: V
authors: Batra
authors: John M
authors: JM
authors: Maris
authors: Min H
authors: MH
authors: Kang
authors: C Patrick
authors: CP
authors: Reynolds
authors: Peter J
authors: PJ
authors: Houghton
authors: Denise
authors: D
authors: Alexander
authors: E Anders
authors: EA
authors: Kolb
authors: Richard
authors: R
authors: Gorlick
authors: Stephen T
authors: ST
authors: Keir
authors: Hernan
authors: H
authors: Carol
authors: Richard
authors: R
authors: Lock
authors: Catherine A
authors: CA
authors: Billups
authors: Malcolm A
authors: MA
authors: Smith
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C484351:EFS protein, human; D007093:Imidazoles; D010750:Phosphoproteins; D011724:Pyridazines; C545188:SGI 1776; D051573:Proto-Oncogene Proteins c-pim-1