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: Vandana Batra, John M Maris, Min H Kang, C Patrick Reynolds, Peter J Houghton, Denise Alexander, E Anders Kolb, Richard Gorlick, Stephen T Keir, Hernan Carol, Richard Lock, Catherine A Billups, Malcolm A Smith
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 59 Issue 4 Pg. 749-52 (Oct 2012) ISSN: 1545-5017 [Electronic] United States
• PMID: 22052829 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Adaptor Proteins, Signal Transducing
• EFS protein, human
• Imidazoles
• Phosphoproteins
• Pyridazines
• SGI 1776
• Proto-Oncogene Proteins c-pim-1

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Cell Line, Tumor (drug effects)
• Cell Proliferation (drug effects)
• Drug Screening Assays, Antitumor
• Imidazoles (pharmacology, therapeutic use)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Neoplasms (metabolism)
• Phosphoproteins (metabolism)
• Proto-Oncogene Proteins c-pim-1 (antagonists & inhibitors, metabolism)
• Pyridazines (pharmacology, therapeutic use)
• Xenograft Model Antitumor Assays