盐酸阿考比芬(Acolbifene Hydrochloride) - 药物靶点：ER_在研适应症：非典型增生，乳腺导管癌，非浸润性导管内癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Acolbifene、Acolbifene hydrochloride (USAN)、阿考比芬

+ [17]

靶点

ER

作用方式

拮抗剂

作用机制

ERs拮抗剂(雌激素受体家族拮抗剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病其他疾病

在研适应症

非典型增生乳腺导管癌非浸润性导管内癌+ [1]

非在研适应症

家族性乳腺癌

原研机构

Endoceutics, Inc.

在研机构

National Cancer Institute

Université Laval

非在研机构

University of Kansas

Endoceutics, Inc.

权益机构

Schering-Plough Corp. USA

Endoceutics, Inc.

最高研发阶段临床2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C29H31NO4

InChIKeyDUYNJNWVGIWJRI-LJAQVGFWSA-N

CAS号182167-02-8

关联

2

项与盐酸阿考比芬相关的临床试验

NCT05941520

/ Recruiting临床2期IIT

Phase IIA Trial of Acolbifene (20 mg) vs Low Dose Tamoxifen (5 mg) in Pre-menopausal Women at High Risk for Development of Breast Cancer

This phase IIA trial compares the effect of acolbifene versus low dose tamoxifen in preventing breast cancer in premenopausal women at high risk for developing breast cancer. The usual approach for patients at increased risk for breast cancer is to undergo yearly breast magnetic resonance imaging or ultrasound in addition to yearly mammogram. Premenopausal women at very high lifetime risk for breast cancer (greater than 50%) can consider preventive removal (mastectomy) of both breasts. Premenopausal women age 35 or older with a prior diagnosis of atypical hyperplasia, lobular carcinoma in situ, or an estimated 10-year risk of greater than or equal to 3% or estimated 10-year risk of greater than or equal to 2-5 times that of the average woman (depending on age) may be advised to consider five years of standard dose tamoxifen. Standard dose tamoxifen is four times the dose used in this study. Estrogen can cause the development and growth of breast cancer cells. Acolbifene and tamoxifen blocks the use of estrogen by breast cells. This study may help researchers measure the effects of acolbifene and low dose tamoxifen on markers of breast cancer risk in mammogram imaging, breast tissue, and in blood samples.

开始日期2024-10-10

申办/合作机构

National Cancer Institute

NCT00853996

/ Completed临床2期IIT

Phase II Study of Acolbifene in Pre-Menopausal Women at High Risk for Breast Cancer

This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back.

开始日期2009-02-01

申办/合作机构

University of Kansas

[+1]

100 项与盐酸阿考比芬相关的临床结果

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100 项与盐酸阿考比芬相关的转化医学

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100 项与盐酸阿考比芬相关的专利（医药）

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48

项与盐酸阿考比芬相关的文献（医药）

2027-02-01·JOURNAL OF ETHNOPHARMACOLOGY

Rapid antidepressant-like effects of Chaihu Shugan San in female restraint-stressed mice: involvement of hippocampal TC2N and ERβ–eNOS–CaMKII–BDNF signaling

Article

作者: Shao, Mengqi ; Lu, Chao ; Jiang, Yiran ; Cheng, Wenqing ; Wu, Lei ; Xiang, Haoke ; Sun, Yan ; Tian, Liyuan ; Zhu, Yaping ; Wei, Zixuan

ETHNOPHARMACOLOGICAL RELEVANCE:

Chaihu Shugan San (CSS), a classical seven-herb formula from the Ming-dynasty text Jing-Yue Quanshu, is widely prescribed for depressive disorders in China. Previous preclinical studies reported antidepressant-like effects only after weeks of repeated administration, mostly in male animals. Whether a single dose of CSS can produce rapid antidepressant-like effects in female animals, and through what mechanism, remains unclear.

AIM OF THE STUDY:

To determine whether a single administration of CSS produces rapid antidepressant-like effects in female mice exposed to chronic restraint stress (CRS), and to explore the underlying hippocampal mechanism.

METHODS AND MATERIALS:

CSS quality was controlled by HPLC quantification of four index components. Female CRS mice received a single dose of CSS (1, 2 or 4 g/kg, i. g.) or ketamine (10 mg/kg, i. p.), followed by behavioral testing (tail suspension, forced swimming, sucrose preference and open field tests) within 2-24 h. Hippocampal RNA sequencing, RT-qPCR, Western blotting and ELISA were used to identify and validate candidate targets; hippocampal AAV-mediated TC2N overexpression and pretreatment with the ERβ antagonist acolbifene or the CaMKII inhibitor KN-93 were used for interventional validation.

RESULTS:

Batch-to-batch variation of the four index components was below 10% (RSDs 3.51-5.66%), with naringin (313.07 ± 11.16 μg/mL) and hesperidin (196.40 ± 11.11 μg/mL) as the major constituents. Acute administration of CSS (2 and 4 g/kg), like ketamine, shortened immobility time in the tail suspension test at 2 h and in the forced swimming test at 12 h, and restored sucrose preference at 24 h, without affecting locomotor activity. Hippocampal transcriptomics identified Tc2n as up-regulated by CRS and down-regulated by CSS, with Esr2, Nos3 and Camk2a showing the opposite pattern; these changes were confirmed at the mRNA and protein levels within 2 h. Hippocampal TC2N overexpression or pretreatment with acolbifene or KN-93 abolished the rapid behavioral effects of CSS and the associated changes in ERβ-eNOS-CaMKII-BDNF signaling.

CONCLUSION:

CSS produces rapid, ketamine-comparable antidepressant-like behavioral effects in female CRS-exposed mice, accompanied by down-regulation of hippocampal TC2N and involvement of ERβ, eNOS, CaMKII and BDNF. Because only female mice were studied, these findings are specific to females and support an estrogen-linked mechanism that warrants confirmation in male animals and further translational study.

2022-03-20·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[Estradiol inhibits differentiation of mouse macrophage into a pro-inflammatory phenotype by upregulating the IRE1α-XBP1 signaling axis].

Article

作者: Wang, S ; Li, X ; Chen, B ; Zhuo, L ; Liu, X

OBJECTIVE:

To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.

METHODS:

Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 μ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-β, IL-6, IL-10 and TNF-α were detected with RT-PCR.

RESULTS:

Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-β (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 μ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-β (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist.

CONCLUSION:

Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.

2020-10-08·Journal of medicinal chemistry1区 · 医学

Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors

1区 · 医学

Article

作者: Cheng, Han ; Xiong, Rui ; Anantpadma, Manu ; Shen, Zhengnan ; Cooper, Laura ; Thatcher, Gregory R. J. ; Li, Yangfeng ; Dye, Katherine ; Nowar, Raghad ; Rong, Lijun ; Medegan Fagla, Bani ; Schafer, Adam ; Davey, Robert A.

Filoviridae, including Ebola (EBOV) and Marburg (MARV) viruses, are emerging pathogens that pose a serious threat to public health. No agents have been approved to treat filovirus infections, representing a major unmet medical need. The selective estrogen receptor modulator (SERM) toremifene was previously identified from a screen of FDA-approved drugs as a potent EBOV viral entry inhibitor, via binding to EBOV glycoprotein (GP). A focused screen of ER ligands identified ridaifen-B as a potent dual inhibitor of EBOV and MARV. Optimization and reverse-engineering to remove ER activity led to a novel compound 30 (XL-147) showing potent inhibition against infectious EBOV Zaire (0.09 μM) and MARV (0.64 μM). Mutagenesis studies confirmed that inhibition of EBOV viral entry is mediated by the direct interaction with GP. Importantly, compound 30 displayed a broad-spectrum antifilovirus activity against Bundibugyo, Tai Forest, Reston, and Měnglà viruses and is the first submicromolar antiviral agent reported for some of these strains, therefore warranting further development as a pan-filovirus inhibitor.

100 项与盐酸阿考比芬相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02758	盐酸阿考比芬	-	DB16080

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
乳腺癌	临床3期	加拿大	Endoceutics, Inc.	2011-08-06
非典型增生	临床2期	美国	National Cancer Institute	2024-10-10
乳腺导管癌	临床2期	美国	National Cancer Institute	2024-10-10
非浸润性导管内癌	临床2期	美国	National Cancer Institute	2024-10-10
家族性乳腺癌	临床2期	美国	University of Kansas	2009-02-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00853996 (CTgov)	临床2期	乳腺癌 \| 家族性乳腺癌	25	acolbifene hydrochloride	壓鹽鹹築鏇遞繭糧艱艱(獵廠繭衊遞齋鑰衊醖鏇) = 鬱壓鹹構壓鑰觸醖鑰觸醖夢鏇廠夢製遞簾鹹積 (衊襯繭糧夢壓淵觸醖襯, 積膚繭窪糧遞觸鑰積遞 ~ 獵憲醖壓築繭鏇醖獵醖) 更多	-	2017-03-13
ASCO2012	N/A	-	25	Acolbifene 20 mg/d	廠艱簾醖憲積廠蓋鹹膚(襯積糧積鑰壓廠鹹襯遞) = 範糧遞繭網製廠齋襯鑰衊糧襯夢構衊廠鏇壓夢 (夢醖顧齋憲簾觸憲遞簾 )	-	2012-05-20