Introduction
The oncogenic potential of PIM kinases
Apoptosis
Cell cycle regulation
Cell Proliferation
Cell migration
Expression levels of PIM kinases in hematologic cancer
Pim kinases as therapeutic targets
Compound | Class | PIM inhibition selectivity | Development | Disease |
---|---|---|---|---|
SGI-1776
| imadizaopyridazine | IC50: 7 nM PIM1, 363 nM PIM2, 69 nM PIM3, 44 nM FLT-3 and 34 nM Haspin [107]. | Failure in phase I clinical trials by cardiotoxicity | Non-Hodgkin lymphoma |
SMI4a
| benzylidene-thiazolidene-2,4-dione | IC50: 21 nM PIM1, 100 nM PIM2 [113]. | Preclinical | Acute myeloid leukemia |
Selective vs. 56 kinases [114]. | ||||
LGB321
| 3-(S)-amino-piperidine pyridyl carboxamide | IC50: 0.001 nM PIM1, 0.0021 nM PIM2, and 0.0008 nM PIM3 [106]. | Recruiting patients for clinical trials | Multiple myeloma |
AZD1897
| IC50: 3 nM PIM1,2 and 3 [115]. | Preclinical | Acute myeloid leukemia | |
SEL24-B58
| Benzoimidazol | IC50: 31 nM PIM1, 154 nM PIM2, 152 nM PIM3. Selective in a panel of 299 kinases with the exception of haspin, HIPK and CLK kinases [117]. | Preclinical | Leukemic monocyte lymphoma |
AZD1208
| thiazolidene | IC50: Pim-1 0.4 nM, Pim-2 5.0 nM and Pim-3 1.9 nM [115]. | Recruiting patients for clinical trials | Acute myeloid leukemia |