ライフサイエンスコーパス: ENT1

1 ENT1 deficiency notably potentiated the therapeutic acti

2 ENT1 deficiency was further associated with decreased tu

3 ENT1 IC(50)-based models were generated from ChEMBL; sub

4 ENT1 inhibition, therefore, augments anti-cancer immune

5 ENT1 is an equilibrative nucleoside transporter that ena

6 ENT1 is colocalized with A1R in mouse and human dorsal r

7 ilibrative nucleoside transporter subtype 1 (ENT1) plays a crucial role in regulating adenosine level

8 s by equilibrative nucleoside transporter 1 (ENT1) and inhibition of de novo pyrimidine nucleotide sy

9 via equilibrative nucleoside transporter 1 (ENT1) homologs.

10 the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracell

11 n of equilibrative nucleoside transporter 1 (ENT1) or concentrative nucleoside transporter 3 (CNT3) i

12 ter, equilibrative nucleoside transporter 1 (ENT1), was associated with the co-occurrence of sleep pr

13 the equilibrative nucleoside transporter 1 (ENT1), which is responsible for adenosine transport acro

14 n of equilibrative nucleoside transporter 1 (ENT1).

15 the equilibrative nucleoside transporter 1 (ENT1, SLC29A1) regulates inosine levels in BAT: ENT1-def

16 the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its abi

17 with equilibrative nucleoside transporter 1 (ENT1; SLC29A1) are known to be affected by cysteine-modi

18 mber equilibrative nucleoside transporter-1 (ENT1) in the regulation of cardiac adenosine levels.

19 y of equilibrative nucleoside transporter-1 (ENT1), the major regulator of extracellular adenosine co

20 the equilibrative nucleoside transporter-1 (ENT1).

21 ENT2 IC(50): 77 uM), followed by EIDD-1931 (ENT1 IC(50): 259 uM; ENT2 IC(50): 467 uM), whereas molnu

22 uilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2) inhibitory activity albeit less potent th

23 ent with synthetic growth defects of pan1-20 ENT1(EE) cells, overexpressing glutamate-substituted Ent

24 ic growth defects were observed in a pan1-20 ENT1(EE) double mutant, suggesting that Ent1p phosphoryl

25 In addition, ENT1 inhibition or knockdown reduces glutamate transport

26 Additionally, ENT1/2 chemical inhibition and ENT1 knockout prevented P

27 o-expressed substance P, IB4 or NF, although ENT1 was most highly expressed in the peptidergic popula

28 Additionally, ENT1/2 chemical inhibition and ENT1 knockout prevented P. aeruginosa-induced lung NLRP3

29 l regulation of ZEB1, ITGA3, ITGB1, JNK, and ENT1 by ZIP4 using chromatin precipitation and luciferas

30 nosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy.

31 nhibitor, nitrobenzylthioinosine (NBTI), and ENT1-null mice, we demonstrated that ENT blockade elevat

32 constructing chimeras between human PMAT and ENT1, we showed that a chimera consisting of transmembra

33 specific to RBV, since transport of another ENT1 substrate, cytidine, was unaffected.

34 dentifying and predicting compounds that are ENT1 and ENT2 substrates and can circumvent the blood-te

35 dentifying and predicting compounds that are ENT1 and ENT2 substrates and can thereby circumvent the

36 ith systematic modification and evaluated as ENT1 inhibitors by flow cytometry.

37 ific nucleoside transporter subtypes such as ENT1 is not established.

38 1, SLC29A1) regulates inosine levels in BAT: ENT1-deficiency increases extracellular inosine levels a

39 r basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intrac

40 Because P. berghei ENT1 (PbENT1) shares only 60% amino acid sequence identi

41 regulated ENT1 upon activation, and blocking ENT1 enhanced their function when cocultured with cognat

42 distribution studies show that mRNA for both ENT1 isoforms are ubiquitously co-expressed in mouse.

43 SLA2 exhibits genetic interactions with both ENT1 and ENT2, and that the clathrin adaptors and Sla2p

44 R2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism.

45 (18)F-FLT is transported into the cell by ENT1 and ENT2, where it is phosphorylated by TK1 and tra

46 hlighting the promise of rationally designed ENT1 inhibitors for non-opioid pain medications.

47 ereas chronic ethanol exposure downregulates ENT1.

48 ffinity K(d) of 0.377 +/- 0.098 nM, and each ENT1 cell has 34,000 transporters with a turnover number

49 e equilibrative nucleoside transporter (ENT) ENT1 or the concentrative nucleoside transporter (CNT) C

50 ave previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum a

51 thanol-sensitive adenosine transporter ENT1 (ENT1(-/-)).

52 ast has two redundant genes encoding epsins, ENT1 and ENT2; deleting both genes is lethal.

53 Next, we exposed ENT1 KO and WT mice to constant light (LL) and found fur

54 to identify inhibitors of the P. falciparum ENT1 (PfENT1) that kill P. falciparum parasites in cultu

55 ble-labeling revealed a punctate pattern for ENT1 closely associated, in some instances, with cell bo

56 dy used three-dimensional pharmacophores for ENT1 and ENT2 substrates and inhibitors and Bayesian mac

57 A specific role for ENT1 in human erythropoiesis was demonstrated by a defec

58 energy provision, identifying a key role for ENT1 proteins in metabolic effects of medium chain fatty

59 zation, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently sugge

60 e triacetate had different IC(50) values for ENT1 and ENT2.

61 recycling to the plasma membrane and forces ENT1 to the lysosome for degradation.

62 In sensory ganglia, ENT1 was localized to a high proportion of cell bodies o

63 of Ado transport is in the order ENT3>=ENT2>ENT1, which also corresponds to the intrinsic ability of

64 Conversely, high ENT1 levels correlated with lower expression of the ther

65 Blocking or deleting host ENT1 significantly enhanced CD8+ T-cell-dependent antitu

66 Ile216Thr loss of function mutation in human ENT1 was associated with significantly lower body mass i

67 egion in the translocation function of human ENT1.

68 In summary, this study identified ENT1-mediated adenosine uptake as an important mechanism

69 These studies identify ENT1 and adenosine receptors as key to the process of re

70 These findings implicate ENT1 in liver protection from ischemia and reperfusion i

71 enyl)methyl]-6-thioinosine (NBMPR) by 30% in ENT1 cells (P = 0.0248) and 27% in ENT2 cells (P = 0.005

72 decreased in the presence of NBMPR by 77% in ENT1 cells (P = 0.0463) and by 64% in ENT2 cells (P = 0.

73 pression and circadian locomotor activity in ENT1 KO mice.

74 We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice we

75 amplitude and reduces ethanol consumption in ENT1-null mice.

76 S and promoted excessive ethanol drinking in ENT1(+/+) mice, but not in ENT1(-/-) mice.

77 ay contribute to increased alcohol intake in ENT1 KO mice.

78 found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that

79 hanol drinking in ENT1(+/+) mice, but not in ENT1(-/-) mice.

80 hich may contribute to alcohol preference in ENT1 KO mice.

81 Q, which possesses the equivalent residue in ENT1, gained uridine transport activity.

82 whereas molnupiravir was a modest inhibitor (ENT1 IC(50): 701 uM; ENT2 IC(50): 851 uM).

83 Tumors inoculated into ENT1-deficient mice showed increased infiltration of eff

84 Here, we investigate ENT1 activity in controlling the effects of two dietary

85 These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, w

86 We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the stri

87 peated CRE sites in both genotypes (CRE-lacZ/ENT1(+/+) mice and CRE-lacZ/ENT1(-/-) mice) and the domi

88 otypes (CRE-lacZ/ENT1(+/+) mice and CRE-lacZ/ENT1(-/-) mice) and the dominant-negative form of CREB,

89 Mechanistically, ENT1-mediated adenosine uptake inhibited the activity of

90 Although the mouse ENT1 (mENT1), expressed in Madin-Darby canine kidney cel

91 alysis of genomic DNA corresponding to mouse ENT1 indicates the isoforms can be produced by alternati

92 ive nucleoside transporter 2 (ENT2), but not ENT1, is capable of translocating BAs across the mammali

93 Electron microscopy analysis of ENT1 expression in lamina II indicated its presence with

94 n brown adipocytes, knockdown or blockade of ENT1 increased extracellular inosine, which enhanced the

95 Furthermore, genetic deletion of ENT1 in mice was associated with reduced erythroid proge

96 Inhibition or deletion of ENT1 reduced the expression of type 2 excitatory amino-a

97 the expression and cellular distribution of ENT1 in rat dorsal horn and sensory ganglia.

98 orin 1, downregulated membrane expression of ENT1 and terminated RBV uptake.

99 7-290)) was used to reveal the expression of ENT1 protein in tissue homogenates of either adult rat d

100 FLI1 inhibitors suppressed the expression of ENT1, ENT2, and TK1 and thus decreased (18)F-FLT PET act

101 cysteine residues in the C-terminal half of ENT1, particularly one or both of those in the fifth int

102 all, our results highlight the importance of ENT1-mediated nucleotide metabolism in erythropoiesis.

103 tion, and that pharmacological inhibition of ENT1 activity leads to an enhanced effect of decanoic ac

104 In mice, pharmacological inhibition of ENT1 as well as global and adipose-specific ablation enh

105 racellular adenosine uptake by inhibition of ENT1/2 would increase adenosine receptor signaling and p

106 wing short hairpin RNA-mediated knockdown of ENT1.

107 associated protein 9 functional knockouts of ENT1 and ENT2 in HeLa S3 cells were generated and charac

108 s, we observed higher expressional levels of ENT1 than ENT2, in conjunction with repression of ENT1 a

109 gered by both fatty acids in the presence of ENT1 activity.

110 es demonstrated time-dependent repression of ENT1 and ENT2 transcript and protein levels during ALI.

111 than ENT2, in conjunction with repression of ENT1 and ENT2 transcript and protein levels following wa

112 The functional significance of ENT1 expression with regard to the homeostatic regulatio

113 lization was also reduced in the striatum of ENT1 null mice.

114 Notably, our ENT1 inhibitor surpasses gabapentin in analgesic efficac

115 action of ticagrelor, inhibition of platelet ENT1 and inverse agonism at the P2Y12R that contribute t

116 We identify EOS301984 as a potent ENT1 antagonist that restores pyrimidine levels in activ

117 s similar in potency to the prototype potent ENT1 inhibitor NBMPR (0.43 nM).

118 (3-MA), and bafilomycin A1 (BafA1) prevented ENT1 degradation and enhanced RBV antiviral activity.

119 of the clathrin heavy chain by HCV prevents ENT1 recycling to the plasma membrane and forces ENT1 to

120 tivity albeit less potent than the prototype ENT1 inhibitor nitrobenzylmercaptopurine riboside (NBMPR

121 Sequence alignment of hENT1, mENT1, and rat ENT1 (rENT1) showed that the PEXN motif of hENT1 was sub

122 ponds to the previously cloned human and rat ENT1 proteins at Ser-254.

123 istant cell lines may compensate for reduced ENT1-mediated nucleoside uptake by increasing the activi

124 s upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition.

125 Our studies reveal ENT1 as a therapeutic target for analgesia, highlighting

126 Significance: ENT1 is a potential therapeutic target to overcome immun

127 his study, immunoblot analysis with specific ENT1 antibodies (anti-rENT1(227-290) or anti-hENT1(227-2

128 Our results suggest that targeting ENT1/2 and NLRP3 inflammasome may be novel strategies fo

129 A)R and A(2B)R, we further demonstrated that ENT1/2 blockade protected against P. aeruginosa -induced

130 in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive co

131 Mechanistically, we found that ENT1-mediated adenosine transport is critical for cyclic

132 Our results indicate that ENT1 antagonists augment oHSV replication in tumor cells

133 Our results indicate that ENT1 has a physiological role in ethanol-mediated behavi

134 We postulate that ENT1 inhibition may enhance extracellular adenosine leve

135 Here we report that ENT1-null mice show reduced hypnotic and ataxic response

136 Thus, our data show that ENT1 regulates the medium chain fatty acid-induced incre

137 ne reduced ethanol drinking, suggesting that ENT1-mediated downregulation of EAAT2 and AQP4 expressio

138 Here, we modify the ENT1 inhibitor dilazep based on its complex X-ray struct

139 )-mediated enhancement of the binding of the ENT1 inhibitor nitrobenzylmercaptopurine riboside (NBMPR

140 ignificantly enhanced in the presence of the ENT1 nucleoside transporter inhibitors dipyridamole and

141 developed through reduced RBV uptake via the ENT1 nucleoside transporter and antiviral efficacy was r

142 We show that genetic ablation of three ENT1 orthologues unexpectedly improves cell proliferatio

143 [(3)H]NBMPR binds to ENT1 cells with a high affinity K(d) of 0.377 +/- 0.098

144 However, in contrast to ENT1 and ENT2, the endogenous and green fluorescent prot

145 lines in which ENT expression was limited to ENT1 or ENT2.

146 e that RBV uptake is restricted primarily to ENT1 in the cell lines examined.

147 king ethanol-sensitive adenosine transporter ENT1 (ENT1(-/-)).

148 d by inhibition of the adenosine transporter ENT1 (type 1 equilibrative nucleoside transporter), whic

149 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer

150 ts expression of the gemcitabine transporter ENT1, so that cells take up smaller amounts of the drug.

151 ed expression of the gemcitabine transporter ENT1, which reduced gemcitabine uptake by pancreatic can

152 sitive, equilibrative nucleoside transporter ENT1 and thus was designated ENT2.

153 tion between SLC29A1 (nucleoside transporter ENT1) expression and potency of nucleoside analogues, az

154 of the equilibrative nucleoside transporter (ENT1) in human red blood cells with a rare Augustine-nul

155 type 1 equilibrative nucleoside transporter (ENT1), drink more ethanol compared with wild-type mice a

156 sitive equilibrative nucleoside transporter (ENT1), incubation with SB203580 or SB203580-iodo elimina

157 type 1 equilibrative nucleoside transporter (ENT1), whereas chronic ethanol exposure downregulates EN

158 sitive equilibrative nucleoside transporter (ENT1).

159 lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1),

160 ed expression of the nucleoside transporters ENT1 and CNT1.

161 Unlike ENT1-3, PMAT mainly functions as a polyspecific organic

162 s and vascular endothelial cells but, unlike ENT1, is virtually absent from the sinoatrial and atriov

163 T cells upregulated ENT1 upon activation, and blocking ENT1 enhanced their f

164 ibitor of ENT-mediated [(3)H]uridine uptake (ENT1 IC(50): 39 uM; ENT2 IC(50): 77 uM), followed by EID

165 Using ENT1/2 pharmacological inhibitor, nitrobenzylthioinosine

166 Clofarabine and cladribine were ENT1 and ENT2 substrates, whereas nevirapine and lexibul

167 rates, whereas nevirapine and lexibulin were ENT1 and ENT2 nontransported inhibitors.

168 It is not known, however, whether ENT1 is important for ethanol intoxication or consumptio

169 However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may cont

170 Immunoperoxidase labeling with ENT1 antibodies produced specific staining in dorsal hor