ライフサイエンスコーパス: PDE4

1 ty toward cAMP-specific phosphodiesterase-4 (PDE4).

2 cAMP-hydrolyzing enzyme phosphodiesterase 4 (PDE4).

3 phosphodiesterase isoforms (PDE2, PDE3, and PDE4).

4 eraction regulates the catalytic activity of PDE4.

5 mine-induced ERK phosphorylates and inhibits PDE4.

6 ating the therapeutic potential of targeting PDE4.

7 the structure of 8a, cocrystallized with the PDE4.

8 nd/or antisense biologicals targeted towards PDE4.

9 trolled by PDE8s working in conjunction with PDE4.

10 (11)C-(R)-rolipram, a selective inhibitor of PDE4.

11 ations in a compartment that is regulated by PDE4.

12 2A receptor-induced cAMP levels, mediated by PDE4.

13 lexes, aberrantly increasing the activity of PDE4.

14 r novel, highly potent inhaled inhibitors of PDE4.

15 CLL cells promoted by inhibitors of PDE7 and PDE4/7 is attenuated by PKA inhibition, occurs via a mit

16 to study the effects of phosphodiesterase 4 (PDE4), a cAMP phosphodiesterase that is phosphorylated a

17 rticipation of the type 4 phosphodiesterase (PDE4), a new role for phosphodiesterase in neural signal

18 he first to demonstrate that brain levels of PDE4, a critical enzyme that regulates cAMP, are decreas

19 d kinase (ERK)-mediated phosphodiesterase 4 (PDE4) activation and accompanied by downregulation of IF

20 nstrate that treatment with the prototypical PDE4 activator compound lowers intracellular cAMP levels

21 PDE4 activator compounds thus have potential as therapeu

22 binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice

23 c impairments, are associated with increased PDE4 activity in humans.

24 t HTT and DISC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific s

25 ctivity decreased with age, and the relative PDE4 activity was lower in patients with permanent atria

26 Inhibition of PDE4 activity with rolipram enhances cAMP accumulation,

27 ering with cAMP signalling through increased PDE4 activity.

28 y and lung inflammation are unrelated to the PDE4 activity.

29 induced cAMP levels in a manner that reduced PDE4 activity.

30 ading phosphodiesterase 4 (PDE4) to regulate PDE4 activity.

31 ologic or pathophysiologic downregulation of PDE4 activity/expression may be causative in a subset of

32 y and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP.

33 Phosphodiesterase type IV (PDE4), an important component of the cyclic adenosine mo

34 re we present seven co-crystal structures of PDE4 and bound inhibitors that show the regulatory domai

35 ate that ethanol-mediated changes in hepatic PDE4 and cAMP levels play a causal role in liver injury

36 vities, and stimulate cAMP-specific PDE3 and PDE4 and cGMP-specific PDE5 activities.

37 lammatory effect may be due to inhibition of PDE4 and histone deacetylase-2 activation, resulting in

38 , It is now recognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clinical be

39 stent with behavioral data showing that both PDE4 and PDE2 are involved in NMDA receptor-mediated mem

40 cAMP and cGMP are selectively hydrolyzed by PDE4 and PDE2, respectively, in rat primary cerebral cor

41 nt inhibition of the cAMP phosphodiesterases PDE4 and PDE8.

42 Inhibition of type 4 phosphodiesterase (PDE4) and elevation of cyclic adenosine monophosphate (c

43 otent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-alpha inhibitor.

44 on of p38alpha MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the block

45 liferation of ADPKD cells than inhibition of PDE4, and inhibition of PDE1 enhanced AVP-induced ERK ac

46 nvariant glutamine and the substrate cAMP in PDE4, and thus suggests that the widely circulated "glut

47 Type 4 phosphodiesterases (PDE4) are key cAMP-hydrolyzing enzymes, and PDE4 inhibit

48 Taken together, our results implicate PDE4 as an important determinant of CFTR activity in air

49 diesterase 1 (PDE1) and phosphodiesterase 4 (PDE4) as well as for their inhibitory activity on cell p

50 The lack of correlation between PDE4 binding and depressive symptoms could reflect the h

51 lead to the existence of over 25 variants of PDE4, broadly classified as long, short, and supershort

52 pression of a modified DISC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and am

53 re, we show that PAN-selective inhibition of PDE4, but not inhibition of PDE3, causes a time- and dos

54 n by formoterol was displaced to the left by PDE4, but not PDE3, inhibition.

55 We propose that inhibition of PDE4 by atropine accounts, at least in part, for the ind

56 that selectively targeted the regulation of PDE4 by Cdk5, produced analogous effects on stress-induc

57 the phosphorylation of phosphodiesterase-4 (PDE4) by cyclin-dependent protein kinase 5 (Cdk5) facili

58 soproterenol, despite the negative effect of PDE4, cAMP accumulation is sufficient for maximal PKA ph

59 (2019) identify a coronin-1-PDE4-cAMP axis that, when perturbed, results in the indu

60 imerization, we show that only long forms of PDE4 can be regulated by this mechanism.

61 5zf, and 5za into the binding pocket of the PDE4 catalytic domain revealed a similar binding profile

62 Inhibition of PDE4 caused a greater increase in basal and vasopressin

63 in (AKAP250) as the central organizer of the PDE4 complex.

64 soluble DISC1 led to dysregulation of DISC1-PDE4 complexes, aberrantly increasing the activity of PD

65 In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic acti

66 ropose that targeting the Cdk5 regulation of PDE4 could be a new therapeutic approach for clinical co

67 Studies with PDE4-deficient macrophages revealed that the IL-1Ra upre

68 te and chronic pharmacological inhibition of PDE4 effectively reversed impaired beta(2) AR-mediated A

69 intracellular cAMP signaling; inhibition of PDE4 enhances memory.

70 r to occupy the solvent-filled pocket of the PDE4 enzyme, we modified the structure of our oral PDE4

71 cells the possibility of expressing numerous PDE4 enzymes, each with unique amino-terminal-targeting

72 Cyclic AMP (cAMP) phosphodiesterase-4 (PDE4) enzymes degrade cAMP and underpin the compartmenta

73 Inhibitors of cAMP-phosphodiesterase 4 (PDE4) exert a number of promising therapeutic benefits,

74 However, PDE4 exists in several isoforms and pan inhibitors canno

75 alcohol consumption in humans alters hepatic PDE4 expression and cAMP signaling and whether inadequat

76 We report here that PDE3 and PDE4 expression levels are lower in human ADPKD tissue a

77 ation of cAMP-degrading phosphodiesterase 4 (PDE4) expression, which compromises normal cAMP signalin

78 The PDE4 family comprises four subtypes, PDE4A, B, C, and D.

79 otide signaling has come from studies on the PDE4 family.

80 The phosphodiesterase 4 (PDE4) family coordinates the degradation of cAMP, leadin

81 rs of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, pla

82 Four PDE4 genes encode more than 20 isoforms.

83 strate that combined inhibition of PDE8s and PDE4 greatly increased PKA activity including phosphoryl

84 tive pulmonary disease (COPD), inhibition of PDE4 has been predicted to have an antiinflammatory effe

85 PDE4 has four subtypes (PDE4A-D) consisting of 25 splice

86 the heterogeneity of the target, given that PDE4 has four subtypes.

87 cyclic nucleotide phosphodiesterase type 4 (PDE4) has aroused scientific attention as a suitable tar

88 lic AMP (cAMP)-specific phosphodiesterase 4 (PDE4) has been proposed as a potential treatment for a s

89 Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splic

90 cause cAMP levels regulate the expression of PDE4 in rat primary cortical cultures, we examined the m

91 C-(R)-rolipram to image phosphodiesterase-4 (PDE4) in unmedicated MDD patients and after 8 weeks of t

92 C-(R)-rolipram to image phosphodiesterase-4 (PDE4) in unmedicated MDD patients and after ~8 weeks of

93 Finally, combined inhibition of PDE8s and PDE4 increased the expression of steroidogenic acute reg

94 s than inhibition of PDE1, and inhibition of PDE4 induced cyst-like dilations in cultured mouse Pkd1(

95 n cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy, whereas increasing cAMP levels

96 rates in the absence of ICS, indicating that PDE4 inhibition alone is sufficient for therapeutic acti

97 -CFTR, the most common mutation found in CF, PDE4 inhibition alone produced minimal channel activatio

98 PDE4 inhibition also increased the frequency of spontane

99 In this concise review, we detail how PDE4 inhibition downmodulates the B-cell receptor (BCR)-

100 weight of their intestines, suggesting that PDE4 inhibition impairs gastric emptying.

101 re two putative cellular mechanisms by which PDE4 inhibition impairs the acquisition of cocaine CPP.

102 ed the abnormal gastric retention induced by PDE4 inhibition in mice under the premise that it may re

103 In non-CF cells, PDE4 inhibition increased CFTR activity under basal cond

104 PDE4 inhibition increased intracellular cAMP and L-type

105 2)-adrenoceptor inactivation determined that PDE4 inhibition increased the potency and doubled the ef

106 Indeed, PDE4 inhibition induced gastric retention in an acute mo

107 Acute gastric retention induced by PDE4 inhibition is alleviated by treatment with the wide

108 This suggests that PDE4 inhibition may act in part through effects on the a

109 nd inhibition in VTA dopamine neurons, while PDE4 inhibition reestablishes the balance between excita

110 Our results show that PDE4 inhibition significantly attenuates ethanol-induced

111 However, PDE4 inhibition strongly amplified the effects of CFTR c

112 as potentiated by PDE3 inhibition but not by PDE4 inhibition.

113 This effect was magnified by dual PDE3 and PDE4 inhibition.

114 pharmacokinetic properties with retention of PDE4 inhibition.

115 ed GI tissue were the predominant actions of PDE4 inhibition.

116 Phosphodiesterase 4 (PDE4) inhibition restores the suppressive effects of 3',

117 Murine DED was induced, after which a PDE4 inhibitor (cilomilast), dexamethasone, cyclosporine

118 ne (15) were both individually linked to the PDE4 inhibitor 4-(3,4-dimethoxy-phenyl)-4a,5,8,8a-tetrah

119 ts that were differentially regulated by the PDE4 inhibitor 6-[3-(dimethylcarbamoyl)benzenesulphonyl]

120 potentiate induction of UCP1 mRNA, whereas a PDE4 inhibitor alone could augment lipolysis, indicating

121 it beyond that achievable by an ICS alone, a PDE4 inhibitor alone, or an ICS/LABA combination therapy

122 ergistic low-dose adenylyl cyclase activator/PDE4 inhibitor combination.

123 concept in the design of a topically acting PDE4 inhibitor for treatment of dermatological diseases.

124 t was abolished by an alpha2 antagonist or a PDE4 inhibitor in both in vivo models.

125 tagonists administered in conjunction with a PDE4 inhibitor may improve both the efficacy and safety

126 n asthma pathophysiology and the efficacy of PDE4 inhibitor medications.

127 Consequently, the degree to which a PDE4 inhibitor potentiated the effect of a given concent

128 wledge of the 3D-structure of zardaverine, a PDE4 inhibitor resembling the structure of 8a, cocrystal

129 The orally active PDE4 inhibitor Roflumilast-n-oxide has been approved for

130 Here we show that pretreatments with the PDE4 inhibitor rolipram attenuated cocaine-induced locom

131 ts are consistent with observations that the PDE4 inhibitor rolipram attenuates ANP-induced increases

132 The PDE4 inhibitor rolipram dose dependently inhibited the I

133 ly, pharmacologic elevation of cAMP with the PDE4 inhibitor rolipram dramatically inhibited optic gli

134 ell populations following treatment with the PDE4 inhibitor rolipram identified a set of up-regulated

135 also show that intra-VTA microinjections of PDE4 inhibitor rolipram impaired the acquisition, but no

136 epressants desipramine and fluoxetine or the PDE4 inhibitor rolipram on the expression of PDE4D was c

137 These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments af

138 livery system that specifically delivers the PDE4 inhibitor rolipram to the liver to avoid central ne

139 otonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram, drugs that produce antidepressa

140 y a TLR7/8/9 inhibitor, by DNase, and by the PDE4 inhibitor rolipram.

141 topical post-inoculation administration of a PDE4 inhibitor suppresses inflammation in this animal mo

142 YM976, a PAN-PDE4 inhibitor that does not efficiently cross the blood

143 Roflumilast, the only PDE4 inhibitor that has reached the market because of th

144 at it required a combination of a PDE3 and a PDE4 inhibitor to fully induce UCP1 mRNA and lipolysis i

145 e report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T

146 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emes

147 102 (20), a potent, selective, and soft-drug PDE4 inhibitor with properties suitable for patient-frie

148 he cAMP-enhancing compounds rolipram (ROL; a PDE4 inhibitor) and Bt2cAMP (a cAMP mimetic) drive caspa

149 quantify the binding of 11C-(R)-rolipram, a PDE4 inhibitor, as an indirect measure of this enzyme's

150 cated pharmacologically with a non-selective PDE4 inhibitor, implicating cAMP signaling by PDE4B in a

151 icacy of roflumilast, a clinically available PDE4 inhibitor, on endotoxin-inducible proinflammatory c

152 inhaled dual phosphodiesterase 3 (PDE3) and PDE4 inhibitor, RPL554 for its ability to act as a bronc

153 oparesis per se, nor did it protect from PAN-PDE4 inhibitor-induced gastroparesis, indicating that ga

154 ive serotonin reuptake inhibitor (SSRI) to a PDE4 inhibitor.

155 The dual PDE4 inhibitor/SSRI 2-{5-[3-(5-fluoro-2-methoxy-phenyl)-

156 The dual PDE4 inhibitor/SSRI 21 also inhibited PDE4D3 with a K(i)

157 , the antidepressant-like effect of the dual PDE4 inhibitor/SSRI 21 showed a 129-fold increase in in

158 The new dual PDE4 inhibitor/SSRI showed antidepressant-like activity

159 The dual PDE4 inhibitor/SSRI was significantly more effective tha

160 selective submicromolar phosphodiesterase-4 (PDE4) inhibitor associated with anti-TNF-alpha propertie

161 cific cyclic AMP (cAMP) phosphodiesterase-4 (PDE4) inhibitor rolipram, but not the cAMP phosphodieste

162 targeting efficiency of phosphodiesterase 4 (PDE4) inhibitor to the lungs for treating acute lung inj

163 Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, became available in late 2016 in the Un

164 ator, and a cAMP-specific phosphodiesterase (PDE4) inhibitor, indicating that this brimonidine effect

165 studies found that the phosphodiesterase 4 (PDE4) inhibitor, roflumilast, reduced exacerbation frequ

166 t atropine acts as an allosteric PDE type 4 (PDE4) inhibitor.

167 may improve both the efficacy and safety of PDE4-inhibitor therapy for chronic inflammatory disorder

168 PDE4 inhibitors also blocked TLR signaling in normal hum

169 -inflammatory therapies using combination of PDE4 inhibitors and glucocorticoids.

170 (PDE4) are key cAMP-hydrolyzing enzymes, and PDE4 inhibitors are considered as immunosuppressors to v

171 However, development of PDE4 inhibitors as memory enhancers has been hampered by

172 , but not mutated, CLL cells from apoptosis, PDE4 inhibitors augmented apoptosis in both subtypes, su

173 In PBMC and CD14-positive monocytes, PDE4 inhibitors blocked IFN-a or TNF-a (but not IL-6) pr

174 type (WT) and Cln3(Deltaex7/8) mice received PDE4 inhibitors daily beginning at 1 or 3 months of age

175 We demonstrate here that PDE4 inhibitors enhance the anti-inflammatory cytokine i

176 long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory de

177 r of airway smooth-muscle contractility, and PDE4 inhibitors have been developed as medications for a

178 PDE4 inhibitors have been shown to regulate the rewardin

179 cribe the successful clinical repurposing of PDE4 inhibitors in B-cell malignancies, and propose that

180 e studies reveal neuroprotective effects for PDE4 inhibitors in Cln3(Deltaex7/8) mice and support the

181 s mirroring the narrow therapeutic window of PDE4 inhibitors in humans.

182 olved in these pharmacological properties of PDE4 inhibitors in the normal animals.

183 provide a rationale for the use of PDE3 and PDE4 inhibitors in the treatment of COPD and asthma wher

184 Future developments of PDE4 inhibitors include extended indications of roflumil

185 ng was produced by structurally distinct PAN-PDE4 inhibitors including Rolipram, Piclamilast, Roflumi

186 e had no effect, the combination of PDE3 and PDE4 inhibitors induced ATF-1/CREB serine 63/133 phospho

187 PDE4 inhibitors induced gastric retention at similar or

188 -2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues.

189 Therefore, administration of PDE4 inhibitors may also protect against and ameliorate

190 These results suggest that PDE4 inhibitors may be of clinical utility in CLL or aut

191 Moreover, PDE4 inhibitors may be used as efficacious therapeutic a

192 Thus, PDE4 inhibitors might ease AHR, but are unlikely to atte

193 The effect of PDE4 inhibitors on cAMP levels, astrocyte and microglial

194 Here, we report that selective PDE4 inhibitors rolipram and Ro 20-1724 blocked I-LTD an

195 PDE4 inhibitors significantly improved motor function in

196 ected into mice, the combination of PDE3 and PDE4 inhibitors stimulated glucose uptake in BAT under t

197 he identification of novel classes of potent PDE4 inhibitors suitable for pulmonary administration.

198 Well-tolerated doses of PDE4 inhibitors that are already in clinical development

199 stem regulation of gastric emptying and that PDE4 inhibitors that are not brain-penetrant may have an

200 y and reduced vascular toxicity over earlier PDE4 inhibitors that lack subtype selectivity.

201 in airway epithelia, and support the use of PDE4 inhibitors to potentiate the therapeutic benefits o

202 nzyme, we modified the structure of our oral PDE4 inhibitors to reach compounds down to picomolar enz

203 -acting, and efficacious preclinical inhaled PDE4 inhibitors with low emetic potential.

204 d States for mild-to-moderate AD, with other PDE4 inhibitors, an agonist of the aryl hydrocarbon rece

205 improve efficacy and reduce side-effects of PDE4 inhibitors, including delivery via the inhaled rout

206 herapeutic window observed in the clinic for PDE4 inhibitors, primarily due to PDE4 mediated side eff

207 d support the hypothesis that agents such as PDE4 inhibitors, which increase activity within the cAMP

208 These results suggest that PDE4 inhibitors, which increase cAMP cascade activity, m

209 side effect of existing active site-directed PDE4 inhibitors, while maintaining biological activity i

210 we describe the optimization of a series of PDE4 inhibitors, with special focus on solubility and ph

211 f this drug to alleviate the side effects of PDE4 inhibitors.

212 thesized a series of phenyl alkyl ketones as PDE4 inhibitors.

213 f heterocycloalkyl esters as potent in vitro PDE4 inhibitors.

214 ain the therapeutic benefits of nonselective PDE4 inhibitors.

215 investigated whether 3 phosphodiesterase-4 (PDE4) inhibitors (rolipram, roflumilast, and PF-06266047

216 degradation, type 4 cAMP phosphodiesterase (PDE4) inhibitors activate cAMP-mediated signaling and in

217 Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a nu

218 ent of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been goi

219 Oral phosphodiesterase 4 (PDE4) inhibitors, such as cilomilast and roflumilast, ha

220 as (3) the development of new molecules with PDE4 inhibitory properties with an improved efficacy/tol

221 DISC1-PDE4 interaction thus modulates organization of the NDE1

222 ed that dual inhibition of p38alpha MAPK and PDE4 is able to synergistically attenuate the excessive

223 PDE4 is critical in controlling cAMP levels and thereby

224 PDE4 is expressed in human atrial myocytes and accounts

225 Because PDE4 is highly expressed in leukocytes and other inflamm

226 PDE4 is the main selective cAMP-metabolizing enzyme in i

227 These data suggest that whereas PDE4 is the major PDE isoform involved in the regulation

228 Cyclic nucleotide phosphodiesterase-4 (PDE4) is a component of signaling pathways involved in t

229 Phosphodiesterase type 4 (PDE4) is a family of enzymes that selectively degrade in

230 Phosphodiesterase 4 (PDE4) is a key cAMP-metabolizing enzyme involved in the

231 Phosphodiesterase 4 (PDE4) is an essential contributor to intracellular signa

232 Phosphodiesterase subtype 4 (PDE4) is particularly abundant in the brain and has been

233 onophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to th

234 DISC1 and PDE4 isoforms are targeted to specific subcellular locat

235 srupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domai

236 y inhibition of only PDE4B, one of the three PDE4 isoforms expressed in macrophages, and it requires

237 unctional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we sho

238 ing a tool for evaluating the action of long PDE4 isoforms in regulating cAMP-mediated cellular proce

239 s, binding site affinities and the DISC1 and PDE4 isoforms involved.

240 e expression and the catalytic activities of PDE4 isoforms to regulate their various functions and ho

241 dent signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that p

242 opted by long, but not by short (monomeric), PDE4 isoforms.

243 PDE4 isotypes and glucocorticoid receptor (GR)-alpha and

244 Dexamethasone reduced all PDE4 isotypes expression and showed additive effects wit

245 PDE4 isotypes were up-regulated by CSE 5% with the conse

246 nhibition of various PDE isozymes, including PDE4, lead to significant increases in EFA levels throug

247 bility of protein kinase A (PKA) to activate PDE4 long isoforms endogenously, and requires a dimeric

248 ecule compound that allosterically activates PDE4 long isoforms.

249 at inhibitors targeting specific subtypes of PDE4 may exhibit differential pharmacological effects an

250 clinic for PDE4 inhibitors, primarily due to PDE4 mediated side effects.

251 Basic studies suggest that PDE4 mediates the effects of several antidepressants.

252 t catabolize cAMP or inhibit its production (PDE4, mGluR3), and by proteins that bind calcium in the

253 , directed interventions aimed at inhibiting PDE4 might be an effective treatment for ALD.

254 Here, we demonstrate that DISC1 and PDE4 modulate NDE1 phosphorylation by cAMP-dependent pro

255 tion of the NDE1/LIS1/NDEL1 complex is DISC1-PDE4 modulated and likely to regulate its neural functio

256 DISC1, PDE4, NDE1, and NDEL1 have each been implicated as genet

257 r of steroidogenesis, both PDE8 isozymes and PDE4 need to be simultaneously targeted.

258 ammation; inhibitors of phosphodiesterase-4 (PDE4), p38 mitogen-activated protein kinase (p38), Janus

259 be more effective, and include inhibitors of PDE4, p38 MAPK and NF-kappaB, but side effects will be a

260 itors of PDE7 (BRL-50481, IR-202) and a dual PDE4/PDE7 inhibitor (IR-284) selectively increase apopto

261 demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for s

262 Conclusion: Increased PDE4 plays a pathogenic role in the development of ALD;

263 Phosphodiesterase-4 (PDE4) plays an important role in mediating memory via th

264 ive inhibitors of type 4 phosphodiesterases (PDE4), protein kinase A (PKA) or PKA/A-kinase anchoring

265 e investigated the contribution of different PDE4 proteins to the generation of this transient respon

266 inhibitors of phosphodiesterase (PDE) 3 and PDE4 provides greater benefits compared with inhibiting

267 e, thereby revealing the structural basis of PDE4 regulation.

268 Inhibition of PDE4 rescues the adrenergic-induced increase in cAMP/PKA

269 ibitors of PDE3 (siguazodan, cilostazol) and PDE4 (rolipram, GSK256066, roflumilast N-oxide) each sen

270 We describe the design of a novel PDE4 scaffold and the exploration of the dual-soft conce

271 Interestingly, the PDE4-selective inhibitor rolipram attenuates the increas

272 otreatment with PF-04957325 plus rolipram, a PDE4-selective inhibitor, synergistically potentiated st

273 This PDE4-specific activator displays reversible, noncompetit

274 PDE4-specific inhibitor rolipram inhibits S. pneumoniae-

275 ur present work shows that expression of the PDE4 subfamily of enzymes is significantly up-regulated

276 ture that describes an emerging role for the PDE4 subfamily of phosphodiesterases in malignancy.

277 idence examining the functional role of each PDE4 subtype across malignancies, looking for common sig

278 5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram.

279 PDE4 subtype nonselective inhibitors produce potent anti

280 ovel findings will aid in the development of PDE4 subtype- or variant-selective inhibitors for treatm

281 PDE4D represents the major PDE4 subtype.

282 ver, the specific involvement of each of the PDE4 subtypes (PDE4A, 4B and 4C) in different categories

283 ling pathways, and establishing the case for PDE4 subtypes as a potential therapeutic target for canc

284 Thus, potentially, any of the four PDE4 subtypes may be targeted individually for therapeut

285 some species-dependence of the regulation of PDE4 subtypes, based on data obtained previously using r

286 d by negative regulator phosphodiesterase 4 (PDE4) that hydrolyzes cAMP.

287 Phosphodiesterase 4 (PDE4), the primary cAMP-hydrolyzing enzyme in cells, is

288 gous molecules expressed on TH2 lymphocytes, PDE4, the histamine 4 receptor, and Janus kinase) or spe

289 ticipated network topology in which ERK uses PDE4 to regulate PKA output during dopamine signaling.

290 Inhibition of phosphodiesterase 4 (PDE4) to increase endothelial cAMP and stabilize the end

291 ISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity.

292 onsistent with the results of basic studies, PDE4 was decreased in unmedicated MDD patients and incre

293 to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP.

294 minimal because of the hydrolysis of cAMP by PDE4, which leads to a small increase in PKA phosphoryla

295 PET imaging of PDE4 with (11)C-(R)-rolipram has been used successfully

296 Inhibition of PDE4 with rolipram enhances cAMP accumulation, but not P

297 domain revealed a similar binding profile to PDE4 with rolipram except that the fluorine atoms of the

298 Inhibiting PDE4 with rolipram reproduces all of the metabolic benef

299 Compound 5v also showed preference for PDE4 with selectivity of >2000-fold over PDE7, PDE9, PDE

300 esis that inhibition of phosphodiesterase 4 (PDE4) with rolipram to increase vascular endothelial cAM