Dermofural(Dermofural) - 药物靶点：DNA x RNA_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

DNA x RNA

作用方式

抑制剂

作用机制

DNA抑制剂(DNA抑制剂)、RNA抑制剂、蛋白质生物合成抑制剂

治疗领域

感染

在研适应症-

非在研适应症

真菌病

原研机构

Universidad Central De Las Villas

在研机构-

非在研机构

Universidad Central De Las Villas

Gilead Sciences, Inc.

权益机构-

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C6H3Br2NO3

InChIKeyMJPPGVVIDGQOQT-UHFFFAOYSA-N

CAS号35950-55-1

关联

4

项与 Dermofural 相关的临床试验

RPCEC00000423

/ Recruiting临床3期IIT

Phase III clinical trial controlled with placebo, randomized, double-blind, for the evaluation of the efficacy and safety of Dermofural® 0.15% ointment as an antibacterial in patients adults with mild infection of diabetic foot ulcers. - EC III: Dermofural® - DFU

开始日期2025-02-27

申办/合作机构-

JPRN-JapicCTI-205279

/ RecruitingN/A

multi-center trial of the efficacy and safety of G-1 in patients with sepsis or septic shock

开始日期2020-10-01

申办/合作机构

JIMRO Co., Ltd.

JPRN-jRCT1080225183

/ CompletedN/A

multi-center trial of the efficacy and safety of G-1 in patients with sepsis or septic shock

开始日期2020-10-01

申办/合作机构

JIMRO Co., Ltd.

100 项与 Dermofural 相关的临床结果

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100 项与 Dermofural 相关的转化医学

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100 项与 Dermofural 相关的专利（医药）

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196

项与 Dermofural 相关的文献（医药）

2025-04-01·Neurochemical Research

G-Protein-Coupled Estrogen Receptor 1 (GPER1) Activation Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Improves Motor Functions in Adult Zebrafish

Article

作者: Uttam, Vivek ; Upadhayay, Shubham ; Kumar, Puneet

Haloperidol (Halo) is a typical antipsychotic medication used to treat schizophrenia, but its long-term treatment causes neurotoxicity, leading to irregular involuntary movements called Tardive Dyskinesia. Raloxifene (Ralo) and fulvestrant (Fulve) are G-protein-coupled estrogen receptor 1 (GPER1) activators and show similar pharmacological properties as identified in 17β-estradiol. It is reported to have anti-oxidant, anti-inflammatory, and anti-apoptotic properties against neurological disorders. Our study aimed to investigate the neuroprotective effect of ralo and fulve against halo-induced neurotoxicity in SHSY-5Y cells and adult zebrafish. In this study, SHSY-5Y cell lines were treated with ralo (0.01 µM), fulve (0.01 µM), G-15 (1 µM), and G-1 (2 µM) 1 h before halo (100 µM) exposure. Moreover, cell viability was analyzed using MTT assay; apoptosis was done using a confocal microscope, and molecular mechanism investigated through Western Blot and qRT-PCR analysis. For in-vivo study, zebrafish were divided into six groups (n = 12). Treatment with ralo and fulve significantly improved the viability of halo-exposed cells, while it was reduced by G15 treatment. Moreover, ralo and fulve substantially reversed ROS generation, and apoptosis by enhancing the qRT-PCR expression of Nrf2/HO-1/Bcl2 and reduced Bax expression in halo-treated cells. In addition, ralo and fulve treatment enhanced GPER1 expression in halo-treated cells, while G15 treatment reduced it. Furthermore, ralo and fulve injections improved total distance travelled, mean speed, and catalepsy-like behaviour, restoring antioxidant activity in halo-treated zebrafish. Findings suggest that ralo and fulve can activate GPER1/Nrf2/HO-1 signaling pathways and show neuroprotection against halo-induced neurotoxicity. It could be used in the management of neurological disorders.

2025-04-01·The Journal of Steroid Biochemistry and Molecular Biology

GPER agonist G-1 activates YAP to induce apoptosis in breast cancer cells

Article

作者: Xin, Xin ; Fan, Xuhong ; Fu, Ze ; Li, Xin ; Chen, Tongsheng ; Wang, Xiaoping ; Zhan, Yongtong

G-1, a G protein-coupled estrogen receptor (GPER)-specific agonist, exhibits anticancer potential in breast cancer cells. This study aims to explore the molecular basis of apoptosis induced by G-1 in MCF-7 and MDA-MB-231 breast cancer cells. Here, we found that G-1 induced cytotoxicity and GPER-dependent apoptosis with PARP cleavage and mitochondrial membrane potential (MMP) loss, as well as nuclear condensation. Fluorescence resonance energy transfer (FRET) analysis in living cells indicated that G-1 effectively disrupted the interaction between large tumor suppressor 1/2 (LATS1/2) and Yes-associated protein (YAP). Furthermore, G-1 reduced YAP phosphorylation levels and promoted its nuclear accumulation. Notably, knockdown of YAP attenuated G-1-induced apoptosis, highlighting the crucial role of YAP in this process. Additionally, FRET analysis revealed that G-1 enhanced the binding of YAP to p73, leading to an increase in Bcl-2-associated X protein (Bax) expression and an induction of apoptosis. In summary, our findings demonstrate that G-1 induces apoptosis through the GPER/YAP/p73-mediated pathway.

2025-04-01·Cancer Research Communications

LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

Article

作者: Zhuang, Richard ; Luke, Wayne ; Garyantes, Tina K. ; Natale, Christopher A. ; Aguirre-Portolés, Cristina ; Mercado, Sophia ; Arnatt, Christopher K. ; Seykora, John T. ; Ridky, Todd W. ; Olayide, Israel

AbstractEstrogen effects in tissue are mediated in part through activation of the surface estrogen receptor G protein–coupled estrogen receptor (GPER), a broadly expressed G protein–coupled receptor that affects a wide range of normal and pathologic processes, including metabolism, vascular health, inflammation, and cancer. A commonly used synthetic and specific GPER agonist, named G-1, antagonizes tumors by promoting cellular differentiation and enhancing tumor immunogenicity. G-1 is a racemic compound, and since its discovery, the question of whether both enantiomers display agonist activity or the agonist activity resides primarily in a single enantiomer has never been fully resolved. Herein, we disclose the isolation of the pure enantiomers of G-1 and determine that the desirable activity resides exclusively in one enantiomer, named LNS8801, whose configuration we have unambiguously determined by single-crystal X-ray structure analysis. Using preclinical models, we show that LNS8801 suppresses cancer in a GPER-dependent manner and that LNS8801 is efficacious when administered orally. Furthermore, we show that GPER is widely, but not ubiquitously, expressed in both normal and malignant human tissues. In addition, an attenuated response to LNS8801 is observed in a common germline coding variant in human GPER. These findings support ongoing human cancer trials with LNS8801 and suggest that the germline GPER genotype may serve as a predictive biomarker of therapeutic response.Significance:GPER is broadly expressed in human tissues and has tumor-suppressive activity. No FDA-approved agents selectively target GPER. LNS8801 is a synthetic, orally bioavailable, enantiomerically pure, GPER agonist with potent anticancer activity in vivo. LNS8801 response is attenuated by a common germline coding variant present in roughly half of humans.

100 项与 Dermofural 相关的药物交易

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