A Phase I/II Dose Escalation Safety and Efficacy Trial of DE-112 Ophthalmic Solution in Subjects With Primary Open-Angle Glaucoma or Ocular Hypertension

To investigate the safety and efficacy of DE-112 in lowering intraocular pressure in subjects with primary open-angle glaucoma or ocular hypertension.

开始日期2011-01-01

申办/合作机构

Santen Pharmaceutical Co., Ltd.

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项与 Evodenoson 相关的文献（医药）

2019-02-01·Brain, Behavior, and Immunity1区 · 医学

A single peri-sciatic nerve administration of the adenosine 2A receptor agonist ATL313 produces long-lasting anti-allodynia and anti-inflammatory effects in male rats

1区 · 医学

Article

作者: Ellis, Amanda ; Rieger, Jayson ; Green Fulgham, Suzanne M ; Watkins, Linda R ; Favret, Jacob ; Patel, Hardik P ; Maier, Steven F ; Duran-Malle, Julissa Chante ; Kwilasz, Andrew J ; Harvey, Lewis O

Neuropathic pain is a widespread problem which remains poorly managed by currently available therapeutics. Peripheral nerve injury and inflammation leads to changes at the nerve injury site, including activation of resident and recruited peripheral immune cells, that lead to neuronal central sensitization and pain amplification. The present series of studies tested the effects of peri-sciatic nerve delivery of single doses of adenosine 2A receptor (A_2aR) agonists on pain and neuroinflammation. The data provide converging lines of evidence supportive that A_2aR agonism at the site of peripheral nerve injury and inflammation is effective in suppressing ongoing neuropathic pain. After A_2aR agonism resolved neuropathic pain, a return of pain enhancement (allodynia) was observed in response to peri-sciatic injection of H-89, which can inhibit protein kinase A, and by peri-sciatic injection of neutralizing antibody against the potent anti-inflammatory cytokine interleukin-10. A_2aR agonist actions at the nerve injury site suppress neuroinflammation, as reflected by decreased release of interleukin-1β and nitric oxide, as well as decreased sciatic expression of markers of monocytes/macrophages and inducible nitric oxide synthase. Taken together, the data are supportive that A_2aR agonists, acting at the level of peripheral nerve injury, may be of therapeutic value in treating chronic pain of neuroinflammatory origin.

2015-10-15·The Journal of Immunology2区 · 医学

Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow

2区 · 医学

Article

作者: Yago, Tadayuki ; Thompson, Linda F ; McEver, Rodger P ; Tsukamoto, Hiroki ; Wang, Ying ; Liu, Zhenghui

AbstractA2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin–dependent slow rolling and chemokine-induced, β2 integrin–dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out,” which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti–β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin–triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases.

2015-05-01·Brain, Behavior, and Immunity1区 · 医学

Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats

1区 · 医学

Article

作者: Sloane, Evan ; Taylor, Frederick R ; Maier, Steven F ; Strand, Keith A ; Rieger, Jayson ; Loram, Lisa C ; Van Dam, Anne-Marie ; Watkins, Linda R

A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in two different models of neuropathic pain in addition to downregulating glial activation markers in the spinal cord. We aimed to determine whether a single intrathecal administration of an A2AR agonist was able to attenuate motor symptoms induced by experimental autoimmune encephalopathy. Two A2AR agonists (CGS21680 and ATL313) significantly attenuated progression of motor symptoms following a single intrathecal administration at the onset of motor symptoms. OX-42, a marker of microglial activation, was significantly attenuated in the lumbar spinal cord following A2AR administration compared to vehicle. Therefore, A2AR agonists attenuate motor symptoms of EAE by acting on A2AR in the spinal cord.

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外链

KEGG	Wiki	ATC	Drug Bank
D10362	-	-	DB12295

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
开角型青光眼	临床2期	美国	Santen, Inc.	2011-01-01
青光眼	临床2期	-	Santen SAS	-
青光眼	临床2期	-	Allergan Ltd. (Ireland)	-
血液肿瘤	临床2期	美国	PGxHealth LLC	-
多发性硬化症	临床2期	美国	PGxHealth LLC	-
神经痛	临床2期	美国	PGxHealth LLC	-