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 thesized a series of phenyl alkyl ketones as PDE4 inhibitors.

7 ain the therapeutic benefits of nonselective PDE4 inhibitors.

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

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

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

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

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

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

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

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

16 PDE4 inhibitors also blocked TLR signaling in normal hum

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

44 PDE4 inhibitors have been shown to regulate the rewardin

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

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

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

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

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

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

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

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

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

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

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

56 Future developments of PDE4 inhibitors include extended indications of roflumil

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

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

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

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

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

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

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

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

65 -2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

80 The PDE4 inhibitor rolipram also increased cAMP levels signi

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

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

83 The PDE4 inhibitor rolipram dose dependently inhibited the I

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

103 PDE4 inhibitors significantly improved motor function in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

129 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emes

130 102 (20), a potent, selective, and soft-drug PDE4 inhibitor with properties suitable for patient-frie

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

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

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