西奥骨化醇(Seocalcitol) - 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

(5Z,7E,22E,24E)-(1S,3R)-26,27-dimethyl-24a-homo-9,10-seco-5,7,10(19),22,24-cholestapentaene-1,3,25-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

肿瘤消化系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

肝细胞癌肝癌胰腺癌+ [1]

原研机构

Leo Pharma, Inc.

在研机构-

非在研机构

Leo Pharma, Inc.

LEO Pharma A/S

Janssen Oncology, Inc.

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

分子式C30H46O3

InChIKeyLVLLALCJVJNGQQ-SEODYNFXSA-N

CAS号134404-52-7

关联

2

项与西奥骨化醇相关的临床试验

NCT00051545 / Terminated临床3期

Seocalcitol Versus Placebo in the Adjuvant Treatment of Hepatocellular Carcinoma. Efficacy of Seocalcitol (EB 1089) Enteric-Coated Capsules (5 ug) or Placebo in Prolonging Time to Relapse Following Intended Curative Resection or Percutaneous Ablative Treatment for Hepatocellular Carcinoma

To evaluate the efficacy of Seocalcitol in prolonging time to relapse following intended curative resection or percutaneous ablative treatment, i.e. percutaneous ethanol injection(s), percutaneous acetic acid injection(s), percutaneous microwave coagulation therapy, or percutaneous radiofrequency ablation for hepatocellular carcinoma (HCC).

开始日期1999-11-01

申办/合作机构

Leo Pharma, Inc.

NCT00051532 / TerminatedN/A

Seocalcitol Versus Placebo in Advanced Hepatocellular Carcinoma. Efficacy of Seocalcitol (EB 1089) Enteric-Coated Capsules (5ug) or Placebo in the Treatment of Patients With Hepatocellular Carcinoma Not Amenable to Curative Treatment

The purpose of the study is to determine whether seocalcitol is effective in the treatment of advanced primary liver cancer (hepatocellular carcinoma [HCC]).

开始日期1999-09-01

申办/合作机构

Leo Pharma, Inc.

100 项与西奥骨化醇相关的临床结果

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100 项与西奥骨化醇相关的转化医学

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100 项与西奥骨化醇相关的专利（医药）

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249

项与西奥骨化醇相关的文献（医药）

2024-09-01·Advances in Medical Sciences

The vitamin D analog EB1089 sensitizes triple-negative breast cancer cells to the antiproliferative effects of antiestrogens

Article

作者: García-Becerra, Rocío ; García-Quiroz, Janice ; Díaz, Lorenza ; Zárate-Pérez, Adriana ; Ordaz-Rosado, David ; Milo-Rocha, Edgar ; León-Del-Rio, Alfonso ; Avila, Euclides ; Cruz-Cázares, Alitzin Pamela

PURPOSEPatients bearing estrogen receptor (ER)α-negative breast cancer tumors confront poor prognosis and are typically unresponsive to hormone therapy. Previous studies have shown that calcitriol, the active vitamin D metabolite, can induce ERα expression in ERα-negative cells. EB1089, a calcitriol analog with reduced calcemic effects, exhibits greater potency than calcitriol in inhibiting cancer cell growth. However, the impact of EB1089 on ERα expression in triple-negative breast cancer (TNBC) cells remains unexplored. This study aims to investigate whether EB1089 could induce functional ERα expression in TNBC cell lines, potentially enabling the antiproliferative effects of antiestrogens.MATERIALS AND METHODSTNBC cell lines HCC1806 and HCC1937 were treated with EB1089, and ERα expression was analyzed using real-time PCR and Western blots. The transcriptional activity of induced ERα was evaluated through a luciferase reporter assay. The antiproliferative effects of tamoxifen and fulvestrant antiestrogens were assessed using the sulforhodamine B assay in the EB1089-treated cells.RESULTSOur findings indicated that EB1089 significantly induced ERα mRNA and protein expression in TNBC cells. Moreover, EB1089-induced ERα exhibited transcriptional activity and effectively restored the inhibitory effects of antiestrogens, thereby suppressing cell proliferation in TNBC cells.CONCLUSIONEB1089 induced the expression of functional ERα in TNBC cells, restoring the antiproliferative effects of antiestrogens. These results highlight the potential of using EB1089 as a promising strategy for re-establishment of the antiproliferative effect of antiestrogens as a possible management for TNBC. This research lays the foundation for potential advancements in TNBC treatment, offering new avenues for targeted and effective interventions.

2023-09-01·Nanomedicine

Ternary Nanocomposite Potentiates The Lysophosphatidic Acid Effect on Human Osteoblast (MG63) Maturation

Article

作者: Elkodous, Mohamed Abd ; Elkhenany, Hoda ; Mansell, Jason Peter

Aim: This study aimed to investigate the potential of ternary nanocomposite (TNC) to support MG63 osteoblast maturation to EB1089-(3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP) cotreatment. Materials & methods: Binary (P25/reduced graphene oxide [rGO]) nanocomposite was prepared, and silver (Ag) nanoparticles were loaded onto the surface to form TNC (P25/rGO/Ag). The influence of TNC on proliferation, alkaline phosphatase activity and osteogenic gene expression was evaluated in a model of osteoblast maturation wherein MG63 were costimulated with EB1089 and FHBP. Results: TNC had no cytotoxic effect on MG63. The addition of TNC to EB1089-FHBP cotreatment enhanced the maturation of MG63, as supported by the greater alkaline phosphatase activity and OPN and OCN gene expression. Conclusion: TNC could serve as a promising carrier for FHBP, opening up possibilities for its application in bone regeneration.

2023-08-22·ACS omega

PRIMA-1^MET Does Not Restore Vitamin D Sensitivity to MDA-MB-231 and MDA-MB-468 Triple-Negative Breast Cancer Cells.

Article

作者: Kotob, Shadi N ; Kelts, Jessica L

Vitamin D is a steroid hormone that causes growth suppression in cultured cells. We had previously discovered that the triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 did not have growth suppression with vitamin D, while MCF-7 did. MCF-7 cells are not triple-negative and have wild-type p53. Both MDA-MB-231 and MDA-MB-468 have mutations in p53 and these mutations were a possible explanation for the lack of growth suppression with vitamin D. Our hypothesis was that reactivation of p53 in the triple-negative cell lines would cause them to become sensitive to vitamin D. We chose to use the small molecule PRIMA-1^MET to reactivate p53 as it has been previously shown to restore function to the p53 mutants present in MB-231 and MB-468. We then measured the ability of vitamin D and its analogues calcipotriol and EB1089 to suppress growth in the presence of PRIMA-1^MET. Here, we show that while PRIMA-1^MET can kill the breast cancer cells investigated in this study, it does not restore their sensitivity to vitamin D or its analogues.

100 项与西奥骨化醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB04258

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
肝细胞癌	临床3期	英国	Leo Pharma, Inc.	1999-11-01
肝细胞癌	临床3期	西班牙	Leo Pharma, Inc.	1999-11-01
肝细胞癌	临床3期	加拿大	Leo Pharma, Inc.	1999-11-01
肝细胞癌	临床3期	意大利	Leo Pharma, Inc.	1999-11-01
肝细胞癌	临床3期	法国	Leo Pharma, Inc.	1999-11-01
肝癌	临床3期	欧盟	LEO Pharma A/S	-
胰腺癌	临床3期	英国	LEO Pharma A/S	-
前列腺癌	临床3期	美国	Janssen Oncology, Inc.	-