宾达利(Bindarit) - 药物靶点：CCL2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Bindarit (USAN/INN)

靶点

CCL2

作用机制

CCL2抑制剂(C-C基序趋化因子-2抑制剂)

治疗领域

免疫系统疾病心血管疾病内分泌与代谢疾病+ [3]

在研适应症-

非在研适应症

白蛋白尿冠状动脉再狭窄糖尿病肾病+ [3]

原研机构

Angelini Pharma, Inc.

在研机构-

非在研机构

Angelini Pharma, Inc.

Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构

分子式C19H20N2O3

InChIKeyMTHORRSSURHQPZ-UHFFFAOYSA-N

CAS号130641-38-2

关联

2

项与宾达利相关的临床试验

NCT01269242 / Completed临床2期

A Pilot Study to Evaluate the Efficacy and Safety of Different Bindarit Dosages in Preventing Stent Restenosis

The main study objective is to assess the efficacy and safety of different bindarit dosages compared to placebo in preventing restenosis, in patients submitted to coronary stenting and using a bare metal stent (Vision BMS, by Abbott).

开始日期2009-01-01

申办/合作机构

Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA

NCT01109212 / Completed临床2期

The Effects of the Association Bindarit + Irbesartan Versus Irbesartan Alone on Albuminuria on Patients With Diabetic Nephropathy. Placebo-controlled Study

The purpose of this study is to determine whether bindarit is effective to reduce albuminuria, compared to placebo, in nephropathic patients treated with irbesartan, as a background therapy.

开始日期2007-03-01

申办/合作机构

Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA

100 项与宾达利相关的临床结果

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100 项与宾达利相关的转化医学

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100 项与宾达利相关的专利（医药）

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80

项与宾达利相关的文献（医药）

2024-10-01·Acta Biochimica et Biophysica Sinica

CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway

Article

作者: Zhang, Ping ; Xiong, Xiaojian ; Zhang, Wei ; Liao, Shu ; Diao, Yunlian ; Li, Junyao ; Guan, Chenxi ; Ying, Ying ; Liu, Fangpeng ; Huang, Shibo

Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.

2024-10-01·Acta Pharmaceutica Sinica B

Choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus

Article

作者: Liu, Wenke ; Wu, Ke ; Hui, Xuhui ; Li, Hanmei ; You, Shenglan ; Cheng, Jian ; Zhu, Lei ; Li, Yue ; Liu, Fei ; Gao, Huile ; Zhang, Huan ; Zhang, Yi ; Wang, Qiguang ; Qi, Xin

The choroid plexus (ChP) serves as the principal origin of cerebrospinal fluid (CSF). CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently. Nevertheless, the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined. In the present study, we elucidate the critical role of macrophages in the pathogenesis of ChP inflammation. Specifically, we identify the chemokine CCL2, released by ChP epithelial cells, recruits CCR2⁺ monocytes to the ChP thereby inciting hydrocephalus pathogenesis. The accumulated ChP macrophages increase the inflammation in ChP epithelial cells through TNF-α/TNFR1/NF-κB signaling cascade, thereby leading to CSF hypersecretion. Strikingly, augmentation of ChP‒CCL2 using an adeno-associated viral approach (AAV) exacerbates macrophage recruitment, activation, and ventriculomegaly in rat PHH models. Systemic application of Bindarit, a specific CCL2 inhibitor, significantly inhibits ChP macrophage infiltration and activation and reduces CSF secretion rate. Furthermore, the administration of CCR2 antagonist (INCB 3284) reduces ChP macrophage accumulation and ventriculomegaly. This study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus.

2024-04-01·Acta Pharmacologica Sinica

Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis

Article

作者: Li, Zhu-Xin ; Hu, Ze-Gang ; Chen, Xiao-Kang ; Zeng, Chun-Yu ; Wang, Wei Eric ; Wang, Feng ; Zhou, Lu ; He, Yan-Ji ; Lu, Bing-Jun ; Li, Liang-Peng ; Wang, Wei ; Xia, Xue-Wei

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 μg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 μM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 μM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.

100 项与宾达利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03116	-	-	DB12739

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
冠状动脉再狭窄	临床2期	意大利	Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA	2009-01-01
白蛋白尿	临床2期	斯洛文尼亚	Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA	2007-03-01
白蛋白尿	临床2期	意大利	Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA	2007-03-01
糖尿病肾病	临床2期	斯洛文尼亚	Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA	2007-03-01
糖尿病肾病	临床2期	意大利	Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - SpA	2007-03-01
狼疮性肾炎	临床2期	意大利	Angelini Pharma, Inc.	-
胰腺炎	临床2期	意大利	Angelini Pharma, Inc.	-
类风湿关节炎	临床2期	意大利	Angelini Pharma, Inc.	-
类风湿关节炎	临床2期	美国	Angelini Pharma, Inc.	-
类风湿关节炎	临床2期	英国	Angelini Pharma, Inc.	-