A Phase IIa study investigating the efficacy and safety of the c-Jun-N-Terminal Kinase (JNK) inhibitor PGL5001 versus placebo administered for up to 5 months with concomitant administration of depot medroxyprogesterone acetate (DMPA) for the treatment of peritoneal and/or ovarian endometriosis with an inflammatory component, prior to surgery. - JADE

开始日期2012-06-11

申办/合作机构-

NCT01630252 / Completed临床2期

A Phase IIa Efficacy and Safety Study of PGL5001 Versus Placebo Administered for up to 5 Months With Concomitant Administration of Depot Medroxyprogesterone Acetate for the Treatment of Peritoneal and/or Ovarian Endometriosis With an Inflammatory Component.

This is a prospective, three-part (Part A1, Part A2 and Part B),Phase II study investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of the JNK inhibitor PGL5001 orally administered for up to 5 months with concomitant DMPA administration for the treatment of laparoscopically diagnosed inflammatory endometriosis. The part A1 is open-label, the parts A2 and B are double-blind.
The target population will be women of reproductive age and suffering from newly diagnosed peritoneal and/or ovarian endometriosis.

开始日期2012-06-01

申办/合作机构

PregLem SA

100 项与 Bentamapimod 相关的临床结果

登录后查看更多信息

100 项与 Bentamapimod 相关的转化医学

登录后查看更多信息

100 项与 Bentamapimod 相关的专利（医药）

登录后查看更多信息

项与 Bentamapimod 相关的文献（医药）

2022-11-02·Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology

State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials

Review

作者: Herman, Mislav ; Mikuš, Mislav ; Zajec, Vendy ; Vitale, Salvatore Giovanni ; Ciebiera, Michał ; Carugno, Jose ; Ćorić, Mario ; D’alterio, Maurizio Nicola ; Puževski, Tomislav ; Angioni, Stefano

Objective: The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain.Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 179 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, seven primary articles met the inclusion criteria. A systematic review of the data was conducted.Results: This review included several, non-hormonal emerging drug therapies for endometriosis-associated pelvic pain. Based on our results, we divided well-founded studies into three subgroups: antiangiogenic agents, immunomodulators, and natural components. Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors.Conclusion: Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration.

2022-09-01·Journal of neurosurgery

Reduction of sporadic and neurofibromatosis type 2–associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801

Article

作者: Clark, J. Jason ; Yates, Charles W. ; Shibata, Seiji B. ; Canady, Franklin J. ; Dougherty, Mark C. ; Hansen, Marlan R.

OBJECTIVE:

Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5ʹ-triphosphate–competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models.

METHODS:

Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees.

RESULTS:

Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment.

CONCLUSIONS:

The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2–associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.

2021-04-01·Journal of cellular and molecular medicine2区 · 医学

AS602801 sensitizes glioma cells to temozolomide and vincristine by blocking gap junction communication between glioma cells and astrocytes

2区 · 医学

ArticleOA

作者: Wang, Hongxin ; Zhang, Shuai ; Gong, Yong ; Li, Zhongfan ; Fan, TianYu ; Xiang, Peng ; Huang, Yunfeng ; Fu, Xing

Abstract:

Previous studies showed that the chemotherapeutic effect of temozolomide (TMZ) and vincristine (VCR) against glioma might be blunted by the co‐culture with astrocytes, and connexin‐43 (CX43) was thought to play a vital role in the communication between glioma cells and astrocytes. In this study, we aimed to investigate the combined chemotherapeutic effect of AS602801 and TMZ/ VCR in glioma cells both. Dye transfer assay was used to evaluate the gap junction activity between U251 cells and astrocytes. Western blot and immunohistochemistry were carried out to analyse the expression of p‐JNK, CX43 and CASP‐3 proteins treated under different conditions. AS602801 significantly suppressed the gap junction activity between U251 cells and astrocytes. The expression of p‐JNK and CX43 was remarkably inhibited by AS602801. TMZ/VCR‐induced apoptosis of glioma cells was effectively enhanced by AS602801 treatment. Accordingly, the inhibitory role of TMZ/VCR in the expression of p‐JNK, CX43 and CASP‐3 in glioma cells was notably restored by AS602801. Furthermore, in a glioma cell xenograft, AS602801 showed an apparent capability to enhance TMZ/VCR‐induced tumour cell apoptosis through altering the expression of p‐JNK, CX43 and CASP‐3. The findings of this study demonstrated that the co‐culture of glioma cells with astrocytes blunted the tumour killing effect of TMZ and VCR. AS602801 down‐regulated CX43 expression by inhibiting JNK. And AS602801 also sensitized glioma cells to TMZ/VCR by blocking the gap junction communication between glioma cells and astrocytes via down‐regulating CX43, indicating its potential role as a novel adjuvant chemotherapeutic agent in the treatment of glioma.

100 项与 Bentamapimod 相关的药物交易

登录后查看更多信息