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Initial testing (stage 1) of SGI‐1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program
Author(s) -
Batra Vandana,
Maris John M.,
Kang Min H.,
Reynolds C. Patrick,
Houghton Peter J.,
Alexander Denise,
Kolb E. Anders,
Gorlick Richard,
Keir Stephen T.,
Carol Hernan,
Lock Richard,
Billups Catherine A.,
Smith Malcolm A.
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.23364
Subject(s) - medicine , in vivo , myeloid leukemia , pim1 , pharmacology , kinase , in vitro , pharmacokinetics , distribution (mathematics) , leukemia , oncology , enzyme , chemistry , biology , biochemistry , mathematical analysis , microbiology and biotechnology , mathematics , serine
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). Pediatr Blood Cancer 2012;59:749–752. © 2011 Wiley Periodicals, Inc.