Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors.

PubWeight™: 0.81‹?›

🔗 View Article (PMC 4570588)

Published in Arthritis Res Ther on September 15, 2015

Authors

Miguel Perez-Aso1, M Carmen Montesinos2, Aránzazu Mediero3, Tuere Wilder4, Peter H Schafer5, Bruce Cronstein6,7

Author Affiliations

1: Department of Medicine, New York University School of Medicine, 550 First Ave., New York, NY, 10016, USA. mperezaso@gmail.com.
2: Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, 46100, Burjassot, Spain. m.carmen.montesinos@uv.es.
3: Department of Medicine, New York University School of Medicine, 550 First Ave., New York, NY, 10016, USA. Aranzazu.MedieroMunoz@nyumc.org.
4: Department of Medicine, New York University School of Medicine, 550 First Ave., New York, NY, 10016, USA.
5: Department of Translational Development, Celgene Corporation, Summit, NJ, USA. pschafer@celgene.com.
6: Department of Medicine, New York University School of Medicine, 550 First Ave., New York, NY, 10016, USA. Bruce.Cronstein@nyumc.org.
7: Division of Translational Medicine, Department of Medicine, New York University School of Medicine, 550 First Avenue, MSB251, New York, NY, 10016, USA. Bruce.Cronstein@nyumc.org.

Articles cited by this

Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature (1998) 9.30

Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev (2004) 3.65

Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res (2006) 2.59

AKAP signaling complexes: getting to the heart of the matter. Trends Mol Med (2006) 2.29

PDE4 inhibitors: current status. Br J Pharmacol (2008) 2.23

The role of the transcription factor CREB in immune function. J Immunol (2010) 2.23

Signalling from adenosine receptors to mitogen-activated protein kinases. Cell Signal (2003) 2.19

Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim Biophys Sin (Shanghai) (2008) 2.04

Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol (2005) 1.98

Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol (2009) 1.89

Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis (2014) 1.88

Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther (2006) 1.82

An angiogenic switch in macrophages involving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors. Am J Pathol (2003) 1.80

cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res (2007) 1.80

The role of cyclic AMP in the cytolytic activity of lymphocytes. J Immunol (1971) 1.78

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A (1991) 1.61

An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr Med Res Opin (2008) 1.49

Anti-inflammatory activities of cAMP-elevating agents: enhancement of IL-10 synthesis and concurrent suppression of TNF production. J Leukoc Biol (1998) 1.30

Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. J Med Chem (2009) 1.24

Identification of cyclic AMP phosphodiesterases 3, 4 and 7 in human CD4+ and CD8+ T-lymphocytes: role in regulating proliferation and the biosynthesis of interleukin-2. Br J Pharmacol (1996) 1.23

The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5'-nucleotidase: findings in a study of ecto-5'-nucleotidase gene-deficient mice. Arthritis Rheum (2007) 1.22

Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology (Oxford) (2003) 1.20

The cyclic AMP-Epac1-Rap1 pathway is dissociated from regulation of effector functions in monocytes but acquires immunoregulatory function in mature macrophages. J Immunol (2006) 1.18

Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cells. Am J Physiol Cell Physiol (2006) 1.17

Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell Signal (2014) 1.16

Phosphodiesterase 4 inhibitors and the treatment of asthma: where are we now and where do we go from here? Drugs (2000) 1.14

Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. Arthritis Res Ther (2010) 1.14

Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. FASEB J (2010) 1.12

Identification of novel monosodium urate crystal regulated mRNAs by transcript profiling of dissected murine air pouch membranes. Arthritis Res Ther (2008) 1.08

The use of methotrexate in rheumatoid arthritis. Semin Arthritis Rheum (2004) 1.04

Update on the therapeutic potential of PDE4 inhibitors. Expert Opin Investig Drugs (2002) 1.03

Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis. Immunopharmacology (2000) 1.03

Apremilast: a novel PDE4 inhibitor in the treatment of autoimmune and inflammatory diseases. Ther Adv Musculoskelet Dis (2010) 1.02

Thalidomide analogs and PDE4 inhibition. Bioorg Med Chem Lett (1998) 1.01

Regulation of inflammation by adenosine. Front Immunol (2013) 1.01

Effect of methotrexate alone or in combination with sulphasalazine on the production and circulating concentrations of cytokines and their antagonists. Longitudinal evaluation in patients with rheumatoid arthritis. Br J Rheumatol (1995) 1.01

Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B. Br J Pharmacol (1999) 1.01

Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages. Proc Natl Acad Sci U S A (2009) 1.00

Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol (1999) 0.98

Phosphodiesterase 4 and its inhibitors in inflammatory diseases. Chang Gung Med J (2012) 0.94

Adenylate cyclase-centred microdomains. Biochem J (2014) 0.90

Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med (2013) 0.88

Activation of EPAC1/2 is essential for osteoclast formation by modulating NFκB nuclear translocation and actin cytoskeleton rearrangements. FASEB J (2014) 0.88

Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther (2014) 0.87

Relationship of soluble interleukin-2-receptor and interleukin-6 with class-specific rheumatoid factors during low-dose methotrexate treatment in rheumatoid arthritis. Rev Rhum Engl Ed (1997) 0.85

Characterization of the inflammatory response to a highly selective PDE4 inhibitor in the rat and the identification of biomarkers that correlate with toxicity. Toxicol Pathol (2006) 0.85

Phosphodiesterase and cyclic adenosine monophosphate-dependent inhibition of T-lymphocyte chemotaxis. Eur Respir J (2000) 0.84

A nude mouse model of hypertrophic scar shows morphologic and histologic characteristics of human hypertrophic scar. Wound Repair Regen (2012) 0.84

Involvement of SAPK/JNK in basic fibroblast growth factor-induced vascular endothelial growth factor release in osteoblasts. J Endocrinol (2003) 0.83

Adenosine A2A receptor (A2AR) is a fine-tune regulator of the collagen1:collagen3 balance. Purinergic Signal (2013) 0.83

Pharmacophore modeling and virtual screening for the discovery of new type 4 cAMP phosphodiesterase (PDE4) inhibitors. PLoS One (2013) 0.80