ライフサイエンスコーパス: PDE4 inhibitor

1 xtent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor.

2 o-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor.

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

4 rgeted for pharmacological intervention with PDE4 inhibitors.

5 f heterocycloalkyl esters as potent in vitro PDE4 inhibitors.

6 ain the therapeutic benefits of nonselective PDE4 inhibitors.

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

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

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

10 In short, our results suggested that PDE4 inhibitor 14h is a strong candidate for the topical

11 The PDE4 inhibitor 2-(4-([2-(5-Chlorothiophen-2-yl)-5-ethyl-

12 tment of cancer cells with a unique specific PDE4D inhibitor, 26B, triggered massive cell death and g

13 bility of these mutants to bind prototypical PDE4 inhibitors [3H]-(R)-rolipram or [3H]RP 73401 was al

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

15 of PDE4A5 to inhibition by the prototypical PDE4 inhibitor 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-

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

17 s: We selected 5 high-affinity and selective PDE4D inhibitors, absent of a nitro group, from our prio

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

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

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

21 PDE4 inhibitors also blocked TLR signaling in normal hum

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

23 eloped method, modifications of potent GSK's PDE4 inhibitor and MSD's potent hNK(1) antagonist were p

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

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

26 sine monophosphate (cAMP) phosphodiesterase (PDE4) inhibitors and other agents that raise intracellul

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

28 ent of CLL cells with rolipram, a prototypic PDE4 inhibitor, and forskolin, an adenylate cyclase acti

29 Roflumilast, the third phosphodiesterase-IV (PDE4) inhibitor approved for use in dermatology, is indi

30 We prioritized a newer PDE4 inhibitor, apremilast, as ideal for repurposing (i.

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

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

33 of 2, 2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described.

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

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

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

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

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

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

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

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

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

43 All 3 are rationally designed PDE4 inhibitors, but roflumilast is the most potent and

44 strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the

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

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

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

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

49 1)-AR antagonist with a phosphodiesterase-4 (PDE4) inhibitor during graded exercise further increased

50 ned the physicochemical principles that make PDE4 inhibitors effective and propose chemical modificat

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

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

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

54 er the discovery of new phosphodiesterase 4 (PDE4) inhibitors for treatment of psoriasis.

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

56 PDE4 inhibitors have been shown to regulate the rewardin

57 A number of PDE4 inhibitors have been used clinically for the treatm

58 y, these data demonstrate that gene specific PDE4 inhibitors have potential as novel therapeutic agen

59 Rationale: Phosphodiesterase-4 (PDE4) inhibitors have demonstrated increased efficacy in

60 Phosphodiesterase-4 (PDE4) inhibitors have the potential to modulate immune r

61 The binding of other PDE4 inhibitors (high- and low-affinity) was also modele

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

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

64 Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assa

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

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

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

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

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

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

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

72 Future developments of PDE4 inhibitors include extended indications of roflumil

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

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

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

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

77 PDE4 inhibitors induced gastric retention at similar or

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

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

80 This structurally unique class of PDE4 inhibitors is markedly different from the known PDE

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

82 The therapeutic effect of PDE4 inhibitors is thought to be related to inhibition o

83 ous alternation tasks) demonstrate that this PDE4D inhibitor is able to enhance memory in AD transgen

84 -2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues.

85 report the discovery of dual M(3) antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatmen

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

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

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

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

90 Our results suggest that PDE4 inhibitors may be used to treat the cognitive dysfu

91 These results suggest that PDE4 inhibitors may induce CLL apoptosis by activating P

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

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

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

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

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

97 In view of the therapeutic potentials of PDE4 inhibitors, our findings provide the rationale for

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

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

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

101 Additionally, we determined that rolipram, a PDE4 inhibitor, reversed CINC-1-induced derangements of

102 In contrast to the pan PDE4 inhibitor roflumilast, the therapeutic dose of both

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

104 ation episode, using the clinically approved PDE4 inhibitor roflumilast.

105 the clinically approved phosphodiesterase 4 (PDE4) inhibitor roflumilast.

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

107 The PDE4 inhibitor rolipram also increased cAMP levels signi

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

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

110 The PDE4 inhibitor rolipram dose dependently inhibited the I

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

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

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

114 Treatment with the PDE4 inhibitor rolipram induces Rap1 activation in B-CLL

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

116 a key downstream effector of DPY30, and the PDE4 inhibitor rolipram preferentially targeted DPY30-ex

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

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

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

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

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

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

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

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

125 hen co-applied with the phosphodiesterase 4 (PDE4) inhibitor rolipram.

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

127 We demonstrate that the prototypical PDE4 inhibitor, rolipram, and a novel one (HT0712) aboli

128 Two prototypical PDE4 inhibitors, rolipram and RP 73401, inhibited cAMP h

129 potential of a specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5

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

131 Unlike other classical PDE4 inhibitors, several analogues were found to be none

132 PDE4 inhibitors significantly improved motor function in

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

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

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

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

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

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

139 ibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3).

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

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

142 In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tu

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

144 To identify determinants of response to the PDE4 inhibitor tanimilast.

145 ibition by rolipram as well as several other PDE4 inhibitors tested.

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

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

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

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

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

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

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

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

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

155 idered in conjunction with ongoing trials of PDE4 inhibitors to treat alcohol withdrawal and reduce a

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

157 y, and then targeted PDE4D activation with a PDE4D inhibitor to define how changes in cAMP levels aff

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

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

160 ports, however, have indicated that specific PDE4 inhibitors were effective in treatment of experimen

161 PDE4 inhibitors were identified as a potential AUD treat

162 he effects resulting from treatment with PAN-PDE4 inhibitors, which have been shown to increase bacte

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

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

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

166 selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory

167 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emes

168 102 (20), a potent, selective, and soft-drug PDE4 inhibitor with properties suitable for patient-frie

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

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

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