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 mine-induced ERK phosphorylates and inhibits PDE4.

5 ating the therapeutic potential of targeting PDE4.

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

7 nd/or antisense biologicals targeted towards PDE4.

8 lexes, aberrantly increasing the activity of 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 r novel, highly potent inhaled inhibitors of PDE4.

14 eraction regulates the catalytic activity of PDE4.

15 cture, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro

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

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

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

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

20 The effect of PDE4 ablation on chemotaxis was comparable, but not addi

21 Inhibitors of phosphodiesterase type 4 (PDE4) act by increasing intracellular concentrations of

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

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

24 myocytes, chronic inhibition of PDE3 but not PDE4 activity by pharmacological agents or adenovirus-de

25 Because PDE4 activity is positively regulated by PKA, our result

26 The increased PDE4 activity is seen as preventing cAMP from inhibiting

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

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

29 Inhibition of PDE4 activity with rolipram enhances cAMP accumulation,

30 ering with cAMP signalling through increased PDE4 activity.

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

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

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

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

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

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

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

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

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

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

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

42 PDE4 and PDE7 have important roles in T cell activation.

43 nt inhibition of the cAMP phosphodiesterases PDE4 and PDE8.

44 n DLBCL and suggest that clinically relevant PDE4 and PI3K/AKT inhibitors might be useful in the trea

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

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

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

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

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

50 ll responses, and type 4 phosphodiesterases (PDE4) are important regulators of this pathway.

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

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

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

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

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

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

57 Consistent with these results, inhibitors of PDE4, but not PDE3, selectively abolished the lateral co

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

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

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

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

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

63 5zf, and 5za into the binding pocket of the PDE4 catalytic domain revealed a similar binding profile

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

65 phosphodiesterases (PDEs), such as PDE3 and PDE4, coexist in cardiomyocytes and elicit differential

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

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

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

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

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

71 intracellular cAMP signaling; inhibition of PDE4 enhances memory.

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

73 that dimerization defines the properties of PDE4 enzymes and suggest a common structural and functio

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

75 ry properties and inhibitor sensitivities of PDE4 enzymes.

76 both subunits is essential to fully activate PDE4 enzymes.

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

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

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 PDE4D is the predominant PDE4 form in tracheal extracts and PDE4D mRNA is express

83 Four PDE4 genes encode more than 20 isoforms.

84 provide evidence that only one of the three PDE4 genes expressed in mouse peritoneal macrophages is

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

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

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

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

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

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

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

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

93 However, the role of PDE3 and PDE4 in the regulation of cardiomyocyte apoptosis remain

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

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

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

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

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

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

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

101 PDE4 inhibition also increased the frequency of spontane

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

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

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

105 PDE4 inhibition increased intracellular cAMP and L-type

106 arrhythmias and dysfunction associated with PDE4 inhibition or deficiency were suppressed in mice ha

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

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

109 Acute PDE4 inhibition with rolipram had additional inhibitory

110 e, but not additive, to the effects of acute PDE4 inhibition with rolipram.

111 pharmacokinetic properties with retention of PDE4 inhibition.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

129 The PDE4 inhibitor rolipram dose dependently inhibited the I

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

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

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

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

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

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

136 ivity of the enzymes toward the prototypical PDE4 inhibitor rolipram.

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

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

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

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

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

142 A 4,000-fold increase in the potency of this PDE4 inhibitor was achieved after only two rounds of che

143 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emes

144 102 (20), a potent, selective, and soft-drug PDE4 inhibitor with properties suitable for patient-frie

145 reover, they provide proof of concept that a PDE4 inhibitor with subtype selectivity retains useful p

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

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

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

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

150 screpant sensitivity of B-CLL and T cells to PDE4 inhibitor-induced apoptosis.

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

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

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

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

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

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

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

158 We now show that the phosphodiesterase 4 (PDE4) inhibitor rolipram (which readily crosses the bloo

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

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

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

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

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

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

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

166 PDE4 inhibitors also blocked TLR signaling in normal hum

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

168 cells uniquely activate Rap1 in response to PDE4 inhibitors and suggest that physiologic stimuli tha

169 mately, clinicians will want to know whether PDE4 inhibitors are anything more than expensive "design

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 utations increase the sensitivity of PDE7 to PDE4 inhibitors but are not sufficient to render the eng

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

176 We describe a family of potent PDE4 inhibitors discovered using an efficient method for

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

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

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

180 PDE4 inhibitors have been shown to regulate the rewardin

181 The emerging results of clinical trials on PDE4 inhibitors in asthma and COPD should be interpreted

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

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

184 The two main orally active PDE4 inhibitors in the late phase III of clinical develo

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

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

187 Future developments of PDE4 inhibitors include extended indications of roflumil

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

189 The therapeutic ratio for PDE4 inhibitors is thought to be determined by selectivi

190 -2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues.

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

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

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

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

195 restricted access is lost in the presence of PDE4 inhibitors or after ablation of PDE4D.

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

197 PDE4 inhibitors significantly improved motor function in

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

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

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

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 heterocycloalkyl esters as potent in vitro PDE4 inhibitors.

212 ain the therapeutic benefits of nonselective PDE4 inhibitors.

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

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

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

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

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

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

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

220 DISC1-PDE4 interaction thus modulates organization of the NDE1

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

222 PDE4 is critical in controlling cAMP levels and thereby

223 PDE4 is expressed in human atrial myocytes and accounts

224 Because PDE4 is highly expressed in leukocytes and other inflamm

225 tches by rolipram and RS25344 indicated that PDE4 is localized in close proximity to the CFTR channel

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

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

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

241 -regulation of specific phosphodiesterase-4 (PDE4) isoforms because of increased histone acetylation.

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

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

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

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

246 3Y/S377T/I412S mutation of PDE7A1 produces a PDE4-like enzyme, implying that multiple elements must w

247 on of dimerization ablates the activation of PDE4 long forms by either protein kinase A phosphorylati

248 rolipram binding, it functions to stabilize PDE4 long forms in their high affinity rolipram binding

249 that the UCR module mediates dimerization of PDE4 long forms, whereas short forms, which lack UCR1, b

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

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

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

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

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

255 Kinetic analysis shows that single PDE7 to PDE4 mutations increase the sensitivity of PDE7 to PDE4

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 ppressed the TNF-alpha response in the other PDE4 null cells.

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

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

261 o a similar subpocket in the active sites of PDE4, PDE5, and PDE9 and has a common pattern of the bin

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

263 rs of HMG-CoA reductase, calcineurin, IMPDH, PDE4, PI-3 kinase, hsp90, and p38 MAPK, among others.

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

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

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

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

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

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

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

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

272 The PDE4 selective inhibitors rolipram and roflumilast had n

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

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

275 PDE4-specific inhibitor rolipram inhibits S. pneumoniae-

276 PDE4 splice variants are classified into long and short

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

278 PDE4 subtype nonselective inhibitors produce potent anti

279 dition, several compounds showed interesting PDE4 subtype specificities, for example, the 3-thienyl d

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

284 Of the four PDE4 subtypes, PDE4D appears to be of particular importa

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

286 rk transiently inhibits phosphodiesterase 4 (PDE4), the enzyme that hydrolyzes cAMP.

287 Phosphodiesterase 4 (PDE4), the major cAMP-specific PDE in inflammatory and i

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

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

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

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

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

293 PDE4 was activated after luminal adenosine exposure in a

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

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

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