伊奈骨化醇(Inecalcitol) - 药物靶点：VDR_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(7E)-19-Nor-9,10-seco-14beta-cholesta-5,7-dien-23-yne-1alpha,3beta,25-triol

靶点

VDR

作用机制

VDR激动剂(维生素D受体激动剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [3]

在研适应症-

非在研适应症

急性髓性白血病慢性淋巴细胞白血病慢性期慢性髓性白血病+ [5]

原研机构

Merck Serono SA

在研机构-

非在研机构

Merck Serono SA

Aton SA

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 (欧盟)

结构

分子式C26H40O3

InChIKeyHHGRMHMXKPQNGF-WNSNRMDMSA-N

CAS号163217-09-2

关联

4

项与伊奈骨化醇相关的临床试验

EUCTR2015-002983-18-ES / Not yet recruiting临床2期

Efficacy Study of Inecalcitol in Combination with Decitabine in Acute Myeloid Leukemia Patients Unfit for Standard Chemotherapy

开始日期2017-09-11

申办/合作机构-

NCT02802267 / Unknown status临床2期

Efficacy Study of Inecalcitol in Combination With Decitabine in Acute Myeloid Leukemia Patients Unfit for Standard Chemotherapy

Evaluate the effect of the addition of inecalcitol to decitabine treatment on overall survival in previously untreated AML patients aged 65 years or more who are randomly assigned to receive decitabine with or without inecalcitol.

开始日期2016-06-01

申办/合作机构

Aton SA

NCT02949570 / Unknown status临床2期

Phase 2 Study to Assess Efficacy and Safety of Inecalcitol in Imatinib-Treated Residual Chronic Myeloid Leukaemia: INIM Study

To assess the efficacy of inecalcitol in combination with imatinib in CML patients with molecular residual disease on imatinib monotherapy.

开始日期2014-02-01

申办/合作机构

Aton SA

100 项与伊奈骨化醇相关的临床结果

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100 项与伊奈骨化醇相关的转化医学

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100 项与伊奈骨化醇相关的专利（医药）

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18

项与伊奈骨化醇相关的文献（医药）

2024-02-01·Saudi Pharmaceutical Journal

Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia

Article

作者: Al-Ali, Luma ; Najdawi, Manal M ; Abu-Irmaileh, Bashaer ; Al-Ani, Raad J ; Abuarqoub, Duaa A ; Saleh, Maysaa M ; Alyoussef Alkrad, Jamal ; Hammad, Alaa M ; Abbas, Manal M ; Naser, Abdallah Y

BackgroundThe use of tyrosine kinase inhibitors (TKIs) as a treatment for chronic myeloid leukemia (CML) has improved the natural history of the disease and increased the duration of survival. Tyrosine kinase inhibitors represent the success of target therapies that work on molecular targets, although some patients still have therapy failure. Vitamin D has antiproliferative, pro-apoptotic, and anti-angiogenic effects on cells, therefore it can be considered as a potential cancer preventative and treatment agent. Inecalcitol (TX-522) is the 14-epi-analogue of Calcitriol (1,25(OH)₂-vitamin D3), and inhibits cancer cell proliferation more effectively than Calcitriol. This study was conducted to evaluate the antiproliferative and synergistic effects of the anticancer drugs Imatinib and Dasatinib in combinations with Inecalcitol on human chronic myeloid leukemia K-562 cells.MethodThe growth inhibitory activities of Inecalcitol, Imatinib, Dasatinib, and different combinations of one of the two drugs (Imatinib and Dasatinib) with Inecalcitol, were determined in vitro using MTT assay against K-562 cell line.ResultsInecalcitol, Imatinib, and Dasatinib showed potent antiproliferative activities against K-562 cells with GI₅₀ values of 5.6 µM, 0.327 µM, and 0.446 nM, respectively. Combinations of Imatinib or Dasatinib with different concentrations of Inecalcitol increased significantly the antiproliferative activities and potencies of both drugs (****p < 0.0001), with optimal GI₅₀ values of 580 pM (Imatinib) and 0.51 pM (Dasatinib). Furthermore, the combination treatments showed synergistic interaction between the antileukemic drugs and Inecalcitol, with combination indices (CI) < 1.ConclusionThe study demonstrated that the human chronic myeloid leukemia K-562 cells were subjected to a synergistic growth inhibitory impact when antileukemic drugs (Imatinib or Dasatinib) were combined with Inecalcitol, therefore, it is recommended that these combinations be viewed as promising novel antileukemic medications and used in place of individual medications with lower dosages and negligible side effects in the treatment of CML.

2017-04-01·Endocrine-Related Cancer2区 · 医学

Vitamin D receptor as a target for breast cancer therapy

2区 · 医学

Article

作者: Gallagher, William ; Duffy, Michael J ; Crown, John ; Synnott, Naoise C ; Klinger, Rut ; Madden, Stephen F ; Murray, Alyson ; O'Connor, Darran ; O'Donovan, Norma

Considerable epidemiological evidence suggests that high levels of circulating vitamin D (VD) are associated with a decreased incidence and increased survival from cancer, i.e., VD may possess anti-cancer properties. The aim of this investigation was therefore to investigate the anti-cancer potential of a low calcaemic vitamin D analogue, i.e., inecalcitol and compare it with the active form of vitamin D, i.e., calcitriol, in a panel of breast cancer cell lines (n = 15). Using the MTT assay, IC50concentrations for response to calcitriol varied from 0.12 µM to >20 µM, whereas those for inecalcitol were significantly lower, ranging from 2.5 nM to 63 nM (P = 0.001). Sensitivity to calcitriol and inecalcitol was higher in VD receptor (VDR)-positive compared to VDR-negative cell lines (P = 0.0007 and 0.0080, respectively) and in ER-positive compared to ER-negative cell lines (P = 0.043 and 0.005, respectively). Using RNA-seq analysis, substantial but not complete overlap was found between genes differentially regulated by calcitriol and inecalcitol. In particular, significantly enriched gene ontology terms such as cell surface signalling and cell communication were found after treatment with inecalcitol but not with calcitriol. In contrast, ossification and bone morphogenesis were found significantly enriched after treatment with calcitriol but not with inecalcitol. Our preclinical results suggest that calcitriol and inecalcitol can inhibit breast cancer cell line growth, especially in cells expressing ER and VDR. As inecalcitol is significantly more potent than calcitriol and has low calcaemic potential, it should be further investigated for the treatment of breast cancer.

2017-04-01·Critical Reviews in Oncology/Hematology2区 · 医学

Vitamin D analogues: Potential use in cancer treatment

2区 · 医学

Review

作者: Murray, Alyson ; O'Donovan, Norma ; Crown, John ; Synnott, Naoise C ; Duffy, Michael J

The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)₂D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers. These associations apply especially in colorectal and breast cancer. Consistent with these findings, calcitriol as well as several of its synthetic analogues have been shown to inhibit tumor cell growth in vitro and in diverse animal model systems. Indeed, some of these vitamin D analogues with low calcemic inducing activity (e.g., EB1089, inecalcitol, paricalcitol) have progressed to clinical trials in patients with cancer. Preliminary results from these trials suggest that these vitamin D analogues have minimal toxicity, but clear evidence of efficacy remains to be shown. Although evidence of efficacy for mono-treatment with vitamin D analogues is currently lacking, several studies have reported that supplementation with calcitriol or the presence of high endogenous circulating levels of vitamin D enhances response to standard therapies.

100 项与伊奈骨化醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB04796

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
急性髓性白血病	临床2期	-	Merck Serono SA	-
急性髓性白血病	临床2期	-	Merck Serono SA	-
慢性淋巴细胞白血病	临床2期	-	Merck Serono SA	-
慢性淋巴细胞白血病	临床2期	法国	Aton SA	-
费城染色体阳性慢性粒细胞白血病	临床2期	-	Merck Serono SA	-
前列腺癌	临床2期	-	Merck Serono SA	-
银屑病	临床2期	欧洲	-	-
银屑病	临床2期	-	Merck Serono SA	-
银屑病	临床2期	法国	Aton SA	-
银屑病	临床2期	美国	-	-

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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


ASCO2011	临床2期	去势抵抗性前列腺癌	54	Inecalcitol	(窪鏇憲衊範鹹鹽築廠範) = 膚製壓網鹽鏇鹹築艱構窪顧膚鑰壓醖膚淵餘憲 (衊簾網範衊構夢窪憲淵 )	-	2011-05-20
710 (AUA2011)	临床2期	去势抵抗性前列腺癌	54	Inecalcitol	(蓋鹹鏇簾壓願憲簾築範) = 餘鏇鏇獵醖鬱糧積構觸觸齋顧憲衊遞餘觸願膚 (鹹鑰糧觸鹽選齋顧襯齋 ) 更多	积极	2011-04-01
ASCO_GU2011	临床2期	去势抵抗性前列腺癌	54	Inecalcitol	(鏇選遞鏇艱餘獵憲襯憲) = 襯糧選構鬱艱積夢糧窪餘鑰窪糧憲選網網廠製 (糧顧網鑰醖鑰簾蓋範選 ) 更多	-	2011-03-01