ENMD-1068, a protease-activated receptor 2 antagonist, inhibits the development of endometriosis in a mouse model

Wang, Yifeng; Lin, Min; Weng, Huinan; Wang, Xuefeng; Yang, Li; Li, Fenghua

doi:10.1016/j.ajog.2014.01.040

Cited by 13 publications

(11 citation statements)

References 40 publications

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“…In vitro, ENMD-1068 has been shown to reduce PAR 2 mediated cell proliferation and to increase apoptosis in human oesophageal adenocarcinoma cells , whilst other studies have reported antiangiogenic and analgesic effects in mouse models of endometriosis and postoperative pain (Oliveira et al, 2013;Wang et al, 2014). Studies utilising GB88 are more limited, however this compound has been shown to antagonise intracellular calcium mobilisation in trypsin treated HT29 cells in vitro and to reduce inflammation in models of arthritis and colitis in vivo (Lohman et al, 2012a;Lohman et al, 2012b;Suen et al, 2012).…”

Section: Par 2 As a Pharmacological Target In Cancermentioning

confidence: 95%

Tumour progression and cancer-induced pain: A role for protease-activated receptor-2?

Kularathna

Pagel

Mackie

2014

The International Journal of Biochemistry & Cell Biology

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Section: Par 2 As a Pharmacological Target In Cancermentioning

confidence: 95%

Tumour progression and cancer-induced pain: A role for protease-activated receptor-2?

Kularathna

Pagel

Mackie

2014

The International Journal of Biochemistry & Cell Biology

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“…The ability of Icon to eliminate pre-existing pathological vessels may provide a novel therapy in endometriosis. A recent study showed that the administration of ENMD-1068, a PAR-2 antagonist, significantly suppresses ectopic endometrial tissue growth in a mouse model revealing another potential novel therapy that targets TF and PAR signaling in treating endometriosis (Wang et al, 2014).…”

Section: Endometriosis and Uterine Hemostasismentioning

confidence: 99%

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding

Schatz

Guzeloglu‐Kayisli

Arlıer

et al. 2016

Hum. Reprod. Update

193

138

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Perivascular decidualized HESCs promote endometrial hemostasis during placentation yet facilitate menstruation through progestational regulation of hemostatic, proteolytic, and vasoactive proteins. Pathological endometrial hemorrhage elicits excess local thrombin generation, which contributes to pLARC associated AUB, endometriosis and adverse pregnancy outcomes through several biochemical mechanisms.

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“…Thus, a reduction in α-SMA and collagen expression and ALT/AST levels observed in fibrotic liver tissues in ENMD-1068-treated mice may partially explain the decreased development of liver fibrosis in these mice. Furthermore, the safety and selectivity of ENMD-1068 has been demonstrated 10, 11, 20 as no mice from the ENMD-1068 50 mg/kg treatment group were observed to have any obvious pathological changes in the abdomen. However, further investigation of the toxicity of ENMD-1068 is warranted.…”

Section: Discussionmentioning

confidence: 99%

ENMD-1068 inhibits liver fibrosis through attenuation of TGF-β1/Smad2/3 signaling in mice

Sun

Wang

Zhang

et al. 2017

Sci Rep

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Protease-activated receptor 2 (PAR-2) plays an important role in the pathogenesis of liver fibrosis. We studied the effect of N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (ENMD-1068), a PAR-2 antagonist, on the development of CCl4-induced liver fibrosis in mice and activation of hepatic stellate cells (HSCs) isolated from the mice. Before CCl4 injection, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control twice per week for 4 weeks. The isolated HSCs were stimulated by TGF-β1 with or without ENMD-1068 to evaluate the role of PAR-2 in TGF-β1 induced HSCs activation and collagen production. We showed that the levels of ALT/AST, collagen content, and α-smooth muscle actin (α-SMA) were significantly reduced by treatment with ENMD-1068 in CCl4-induced fibrotic mice. Interestingly, we found TGF-β1 signaling-related expression levels of α-SMA, type I and III collagen, and C-terminal phosphorylation of Smad2/3 were significantly decreased in the ENMD-1068 treated HSCs. Moreover, we showed ENMD-1068 treatment inhibited trypsin or SLIGRL-NH2 stimulated calcium release and TGF-β1 induced Smad transcriptional activity in HSCs. We demonstrated that ENMD-1068 reduces HSCs activation and collagen expression through the inhibiton of TGF-β1/Smad signal transduction.

show abstract

ENMD-1068, a protease-activated receptor 2 antagonist, inhibits the development of endometriosis in a mouse model

Cited by 13 publications

References 40 publications

Tumour progression and cancer-induced pain: A role for protease-activated receptor-2?

Tumour progression and cancer-induced pain: A role for protease-activated receptor-2?

The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding

ENMD-1068 inhibits liver fibrosis through attenuation of TGF-β1/Smad2/3 signaling in mice

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