ライフサイエンスコーパス: Pim kinase

1 to-oncogene protein), a downstream target of Pim kinases.

2 emonstrated that it has high selectivity for Pim kinases.

3 om apoptosis in Abl transformants expressing Pim kinases.

4 ulation of the stability and function of the Pim kinases.

5 n structures leads to a hypothesis as to how Pim kinase activity might be regulated in vivo.

6 Like the rapamycin target TOR, the Pim kinases also contribute to the regulation of lymphoc

7 uman prostate cancer where overexpression of Pim kinases and antiapoptotic Bcl-2 family members drive

8 Finally, coexpression of the Pim kinases and c-Myc enhances the transforming activity

9 chanism underlying the synergism between the Pim kinases and c-Myc in tumorigenesis.

10 The Akt and Pim kinases are cytoplasmic serine/threonine kinases tha

11 and the JAK/STAT-dependent induction of the Pim kinases are examples of partially overlapping surviv

12 Although PIM kinases are expressed more in Th1 than Th2 cells, we

13 Pim kinases are found to be highly expressed in leukemia

14 Pim kinases are highly homologous to one another and sha

15 Pim kinases are implicated in several leukaemias and can

16 Pim kinases are involved in B-cell development and are o

17 In addition, Pim kinases are involved in modification of SOCS-1 and i

18 The serine/threonine Pim kinases are overexpressed in solid cancers and hemat

19 Thus, PIM kinases are promising therapeutic targets in cHL.

20 Thus, endogenous levels of the Pim kinases are required for T cells to mount an immune

21 Pim kinases are Ser/Thr kinases with multiple substrates

22 ciates with the Pim kinases in vivo, and the Pim kinases are substrates of PP2A phosphatase activity

23 The serine/threonine Pim kinases are up-regulated in specific hematologic neo

24 tion site for Moloney murine leukemia virus (Pim) kinases are serine/threonine/tyrosine kinases and o

25 In summary, we have identified PIM kinases as new regulators of human primary Th1 cell

26 g synthetic lethal interactions with Akt and PIM kinases as suitable for future consideration for cli

27 Collectively these data demonstrate Pim kinases as therapeutic targets in MCL.

28 In the absence of the Pim kinases, c-Myc transduction permitted K-Ras(G12V)-in

29 Pim kinases control the translation of antiapoptotic pro

30 Inhibition of PIM kinases decreases RS cell viability and disrupts sig

31 lationship between myocardial senescence and Pim kinases deserves attention because Pim-1 kinase is c

32 Inhibition of Pim kinases enhanced cell death triggered by short-term

33 Here, we show that PIM kinase expression can affect the clinical outcome of

34 and identified a new function for the entire PIM kinase family in T lymphocytes.

35 riple knockout mice, where all 3 isoforms of Pim kinase family members are genetically deleted.

36 fects resulting from genetic deletion of all Pim kinase family members could provide important insigh

37 als from IL-7 and RAG DSBs activate distinct Pim kinase family members that have context-dependent ac

38 , which encodes an ortholog of the mammalian Pim kinase family.

39 We hypothesize that Pim kinase function can be inhibited by SGI-1776 in MCL

40 tion, we evaluated the effect of SGI-1776 on Pim kinase function.

41 apoptosis and we investigated its effect on Pim kinase functions.

42 Deficiency of the Pim kinase genes is well tolerated in vivo, suggesting t

43 Three isoforms of Pim kinases have been identified and are known to phosph

44 Although Pim kinases have been implicated in cap-dependent transl

45 arated by a non-conserved residue, but they (Pim kinases) have <30% sequence identity with other kina

46 Taken together, our data indicate that PIM kinases in cHL exhibit pleiotropic effects, orchestr

47 We have examined the role of Pim kinases in v-Abl-mediated transformation.

48 atalytic subunit of PP2A associates with the Pim kinases in vivo, and the Pim kinases are substrates

49 Pim kinases inhibit the expression of Bcl-XS.

50 ults underscore the therapeutic potential of Pim kinase inhibition for the treatment of AML.

51 Pim kinase inhibition may be a new strategy for AML trea

52 to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer pati

53 , we investigated the cooperative effects of Pim kinase inhibition with ABT-737, a small molecule ant

54 ukemia (AML) blasts and we hypothesized that Pim kinase inhibition would affect AML cell survival.

55 We hypothesized that Pim kinase inhibition would affect B-cell survival.

56 s in diverse AML cell lines treated with pan-PIM kinase inhibitor and fms-related tyrosine kinase 3 (

57 Treatment with the pan-PIM kinase inhibitor AZD1208 impaired the growth of both

58 tarting from the reported aminopiperidyl pan PIM kinase inhibitor compound 3, a strategy to improve t

59 ical profile of the potent and selective pan PIM kinase inhibitor compound 8 (PIM447) are described.

60 Thus, a pan-Pim kinase inhibitor is highly desirable.

61 tent, highly selective, and orally available Pim kinase inhibitor that effectively inhibits all three

62 SGI-1776 is a small molecule and Pim kinase inhibitor with selectivity for Pim-1.

63 ne marrow from a phase I clinical trial of a Pim kinase inhibitor, AZD1208.

64 Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the

65 These novel Pim kinase inhibitors efficiently interrupted the phosph

66 sed to develop a superior method to evaluate Pim kinase inhibitors featuring label-free determination

67 Small-molecule PIM kinase inhibitors halted the growth of human TN tumo

68 Our findings warrant clinical evaluation of PIM kinase inhibitors in patients with TN tumors that ha

69 umorigenesis and therapeutic resistance, yet Pim kinase inhibitors seem to have only limited effects

70 Overall, these compounds are new Pim kinase inhibitors that may provide leads to novel an

71 tic agents and targeted compounds, including PIM kinase inhibitors.

72 vant predictive biomarker for sensitivity to PIM kinase inhibitors.

73 ylation of AR was reduced in the presence of PIM kinase inhibitors.

74 ed herein demonstrate that expression of the Pim kinases is additionally regulated at the post-transl

75 Upregulation of Pim kinases is observed in several types of leukemias an

76 e-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymp

77 These data suggest that the Pim kinases may regulate cytokine-induced JAK-STAT signa

78 These results demonstrate the Pim kinase-mediated control of energy metabolism and thu

79 ally mediated by phosphorylation of c-Myc by Pim kinase on a novel site, Ser329.

80 to resolve the contributions of Akt/mTOR and Pim kinase pathways to BLyS-mediated survival.

81 Additionally, the Pim kinases phosphorylate Mdm2 in vitro and in cultured

82 tion site for Moloney murine leukemia virus (PIM) kinases PIM1 and PIM2 have been implicated in the c

83 Together, these data suggest that Pim kinases play a key role in the v-Abl transformation,

84 Pim kinases prevent premature cardiac aging and maintain

85 For example, the AKT and PIM kinases produce parallel oncogenic signals and share

86 rom human primary Th cells also suggest that PIM kinases promote the production of IFNgamma, the hall

87 Furthermore, Pim kinases regulate the proapoptotic proteins Bcl-XS an

88 Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47

89 re, we exploit a protein nanopore sensor for Pim kinases that bears a pseudosubstrate peptide attache

90 nction were reduced by inhibition of mTOR or Pim kinases, translation initiation complex assembly, or

91 c fibroblasts (MEFs) deficient for all three Pim kinases [triple knockout (TKO) MEFs] demonstrated ac

92 The endogenous function of the Pim kinases was not restricted to the regulation of cell

93 tors, genetic or pharmacologic inhibition of Pim kinases was sufficient to restore sensitivity in vit

94 Coexpression of the Pim kinases with Socs-1 results in phosphorylation and s

95 m inhibitors that potently inhibit all three Pim kinases with subnanomolar to low single-digit nanomo

96 iation rate constants for the interaction of Pim kinases with their consensus substrate Pimtide (~10(