1 ulation of the stability and function of the
Pim kinases.
2 to-oncogene protein), a downstream target of
Pim kinases.
3 emonstrated that it has high selectivity for
Pim kinases.
4 om apoptosis in Abl transformants expressing
Pim kinases.
5 ncodes viral genes that promote and maintain
Pim kinase activation, which in turn may stimulate T-cel
6 n structures leads to a hypothesis as to how
Pim kinase activity might be regulated in vivo.
7 Like the rapamycin target TOR, the
Pim kinases also contribute to the regulation of lymphoc
8 uman prostate cancer where overexpression of
Pim kinases and antiapoptotic Bcl-2 family members drive
9 Finally, coexpression of the
Pim kinases and c-Myc enhances the transforming activity
10 chanism underlying the synergism between the
Pim kinases and c-Myc in tumorigenesis.
11 Pim kinases are a family of constitutively active serine
12 The Akt and
Pim kinases are cytoplasmic serine/threonine kinases tha
13 We show that the
PIM kinases are dispensable for antigen-receptor and IL-
14 and the JAK/STAT-dependent induction of the
Pim kinases are examples of partially overlapping surviv
15 Although
PIM kinases are expressed more in Th1 than Th2 cells, we
16 Pim kinases are found to be highly expressed in leukemia
17 Pim kinases are highly homologous to one another and sha
18 Pim kinases are implicated in several leukaemias and can
19 Pim kinases are involved in B-cell development and are o
20 In addition,
Pim kinases are involved in modification of SOCS-1 and i
21 The serine/threonine
Pim kinases are overexpressed in solid cancers and hemat
22 Thus,
PIM kinases are promising therapeutic targets in cHL.
23 Thus, endogenous levels of the
Pim kinases are required for T cells to mount an immune
24 Pim kinases are Ser/Thr kinases with multiple substrates
25 ciates with the Pim kinases in vivo, and the
Pim kinases are substrates of PP2A phosphatase activity
26 The serine/threonine
Pim kinases are up-regulated in specific hematologic neo
27 tion site for Moloney murine leukemia virus (
Pim) kinases are serine/threonine/tyrosine kinases and o
28 Together, these data indicate
PIM kinases as important effectors of IEL responses to i
29 In summary, we have identified
PIM kinases as new regulators of human primary Th1 cell
30 g synthetic lethal interactions with Akt and
PIM kinases as suitable for future consideration for cli
31 Collectively these data demonstrate
Pim kinases as therapeutic targets in MCL.
32 M blockade, we comprehensively characterized
PIM kinase-
associated prosurvival functions in DLBCL and
33 In the absence of the
Pim kinases,
c-Myc transduction permitted K-Ras(G12V)-in
34 Inhibition of
PIM kinases caused excessive mitochondrial fission and s
35 Pim kinases control the translation of antiapoptotic pro
36 One key insight was that
PIM kinases controlled the migratory capabilities of eff
37 Inhibition of
PIM kinases decreases RS cell viability and disrupts sig
38 lationship between myocardial senescence and
Pim kinases deserves attention because Pim-1 kinase is c
39 Strikingly,
PIM kinases did not have a dominant impact on IL-2-drive
40 Inhibition of
Pim kinases enhanced cell death triggered by short-term
41 This review takes a closer look at
Pim kinase expression and involvement in hematopoietic c
42 Here, we show that
PIM kinase expression can affect the clinical outcome of
43 and identified a new function for the entire
PIM kinase family in T lymphocytes.
44 riple knockout mice, where all 3 isoforms of
Pim kinase family members are genetically deleted.
45 fects resulting from genetic deletion of all
Pim kinase family members could provide important insigh
46 als from IL-7 and RAG DSBs activate distinct
Pim kinase family members that have context-dependent ac
47 , which encodes an ortholog of the mammalian
Pim kinase family.
48 We hypothesize that
Pim kinase function can be inhibited by SGI-1776 in MCL
49 tion, we evaluated the effect of SGI-1776 on
Pim kinase function.
50 apoptosis and we investigated its effect on
Pim kinase functions.
51 Deficiency of the
Pim kinase genes is well tolerated in vivo, suggesting t
52 In addition, we found that
Pim kinases have a new role during HTLV-1 infection.
53 Three isoforms of
Pim kinases have been identified and are known to phosph
54 Although
Pim kinases have been implicated in cap-dependent transl
55 Pim kinases have been targets of interest for a number o
56 Therefore,
Pim kinases have not only pro-oncogenic roles but also f
57 arated by a non-conserved residue, but they (
Pim kinases)
have <30% sequence identity with other kina
58 The goal of this study was to determine how
PIM kinases impact mitochondrial dynamics, ROS productio
59 Taken together, our data indicate that
PIM kinases in cHL exhibit pleiotropic effects, orchestr
60 In addition, a role for
Pim kinases in control of virus expression and viral lat
61 This study reveals a selective role of
PIM kinases in IL-2 control of CD8 T cells and highlight
62 PIM inhibitors and therapeutic targeting of
PIM kinases in lymphomas.
63 of research has recognized a solid role for
Pim kinases in lymphoproliferative disorders.
64 The expression of
PIM kinases in PMBL diagnostic biopsy specimens was asse
65 We have examined the role of
Pim kinases in v-Abl-mediated transformation.
66 atalytic subunit of PP2A associates with the
Pim kinases in vivo, and the Pim kinases are substrates
67 Pim kinases inhibit the expression of Bcl-XS.
68 efficacy in human clinical trials validated
Pim kinase inhibition as a promising therapeutic approac
69 ults underscore the therapeutic potential of
Pim kinase inhibition for the treatment of AML.
70 Pim kinase inhibition may be a new strategy for AML trea
71 Current studies suggest that
Pim kinase inhibition may be most valuable when accompan
72 to be tested in humans to assess whether pan
PIM kinase inhibition may provide benefit to cancer pati
73 , we investigated the cooperative effects of
Pim kinase inhibition with ABT-737, a small molecule ant
74 ukemia (AML) blasts and we hypothesized that
Pim kinase inhibition would affect AML cell survival.
75 We hypothesized that
Pim kinase inhibition would affect B-cell survival.
76 s in diverse AML cell lines treated with pan-
PIM kinase inhibitor and fms-related tyrosine kinase 3 (
77 Treatment with the pan-
PIM kinase inhibitor AZD1208 impaired the growth of both
78 tarting from the reported aminopiperidyl pan
PIM kinase inhibitor compound 3, a strategy to improve t
79 ical profile of the potent and selective pan
PIM kinase inhibitor compound 8 (PIM447) are described.
80 Thus, a pan-
Pim kinase inhibitor is highly desirable.
81 tent, highly selective, and orally available
Pim kinase inhibitor that effectively inhibits all three
82 orally bioavailable, and well tolerated pan-
Pim kinase inhibitor that proved efficacious in RPMI8226
83 SGI-1776 is a small molecule and
Pim kinase inhibitor with selectivity for Pim-1.
84 ne marrow from a phase I clinical trial of a
Pim kinase inhibitor, AZD1208.
85 Here, we find that a novel
Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the
86 ical trials and in vitro characterization of
Pim kinase inhibitors are examined and future directions
87 and solid tumor cancers, which suggests that
Pim kinase inhibitors could provide patients with therap
88 These novel
Pim kinase inhibitors efficiently interrupted the phosph
89 sed to develop a superior method to evaluate
Pim kinase inhibitors featuring label-free determination
90 Small-molecule
PIM kinase inhibitors halted the growth of human TN tumo
91 Our findings warrant clinical evaluation of
PIM kinase inhibitors in patients with TN tumors that ha
92 umorigenesis and therapeutic resistance, yet
Pim kinase inhibitors seem to have only limited effects
93 Overall, these compounds are new
Pim kinase inhibitors that may provide leads to novel an
94 tic agents and targeted compounds, including
PIM kinase inhibitors.
95 vant predictive biomarker for sensitivity to
PIM kinase inhibitors.
96 ylation of AR was reduced in the presence of
PIM kinase inhibitors.
97 ed herein demonstrate that expression of the
Pim kinases is additionally regulated at the post-transl
98 Upregulation of
Pim kinases is observed in several types of leukemias an
99 e-2, 4-dione small molecule inhibitor of the
Pim kinases,
kills a wide range of both myeloid and lymp
100 an interesting approach since knock-down of
Pim kinases leads to non-fatal phenotypes in vivo sugges
101 The loss of Tax expression triggered by
Pim kinases led to loss in Tax-mediated transactivation
102 ernberg and PMBL cells, we hypothesized that
PIM kinases may be overexpressed in PMBL and involved in
103 phocytes (CTL) target, our data suggest that
Pim kinases may play an important role in immune escape
104 These data suggest that the
Pim kinases may regulate cytokine-induced JAK-STAT signa
105 These results demonstrate the
Pim kinase-
mediated control of energy metabolism and thu
106 Taken together, our data indicate that
PIM kinases modulate the signaling output of different N
107 ally mediated by phosphorylation of c-Myc by
Pim kinase on a novel site, Ser329.
108 ic findings, we combined AZD4573 with either
PIM kinase or PI3K inhibitors.
109 to resolve the contributions of Akt/mTOR and
Pim kinase pathways to BLyS-mediated survival.
110 Additionally, the
Pim kinases phosphorylate Mdm2 in vitro and in cultured
111 have previously reported that the oncogenic
PIM kinases phosphorylate Notch1 and Notch3.
112 tion site for Moloney murine leukemia virus (
PIM) kinases PIM1 and PIM2 have been implicated in the c
113 Together, these data suggest that
Pim kinases play a key role in the v-Abl transformation,
114 Pim kinases prevent premature cardiac aging and maintain
115 For example, the AKT and
PIM kinases produce parallel oncogenic signals and share
116 rom human primary Th cells also suggest that
PIM kinases promote the production of IFNgamma, the hall
117 STAT and tyrosine kinase receptor signaling,
Pim kinases regulate cell proliferation, survival, metab
118 Furthermore,
Pim kinases regulate the proapoptotic proteins Bcl-XS an
119 Targeting
Pim kinases represents an interesting approach since kno
120 tion site for Moloney murine leukemia virus (
PIM) kinases,
specifically PIM3, play a role in hepatobl
121 Phosphorylation of traditional
Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47
122 re, we exploit a protein nanopore sensor for
Pim kinases that bears a pseudosubstrate peptide attache
123 nction were reduced by inhibition of mTOR or
Pim kinases,
translation initiation complex assembly, or
124 c fibroblasts (MEFs) deficient for all three
Pim kinases [
triple knockout (TKO) MEFs] demonstrated ac
125 The endogenous function of the
Pim kinases was not restricted to the regulation of cell
126 tors, genetic or pharmacologic inhibition of
Pim kinases was sufficient to restore sensitivity in vit
127 Inhibition of
PIM kinases was toxic to PMBL cells, attenuated protein
128 Inhibition of
PIM kinases was toxic to PMBL cells, attenuated protein
129 PIM kinases were also needed for IL-2 to sustain high ex
130 PIM kinases were tightly coexpressed with MYC in diagnos
131 Coexpression of the
Pim kinases with Socs-1 results in phosphorylation and s
132 m inhibitors that potently inhibit all three
Pim kinases with subnanomolar to low single-digit nanomo
133 iation rate constants for the interaction of
Pim kinases with their consensus substrate Pimtide (~10(