更新于：2024-11-21

AD-047

更新于：2024-11-21

概要

研发状态

概要

基本信息

药物类型

小分子化药

别名

靶点-

作用机制-

治疗领域

神经系统疾病呼吸系统疾病

在研适应症

睡眠呼吸暂停综合征

非在研适应症-

原研机构

Apnimed, Inc.初创企业

在研机构

Apnimed, Inc.初创企业

非在研机构-

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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关联

项与 AD-047 相关的临床试验

ACTRN12618001181291 / Completed临床1/2期

The effects of AD047 and AD282 on obstructive sleep apnoea (OSA)

开始日期2018-08-13

申办/合作机构

Apnimed, Inc.初创企业

100 项与 AD-047 相关的临床结果

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100 项与 AD-047 相关的转化医学

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100 项与 AD-047 相关的专利（医药）

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项与 AD-047 相关的文献（医药）

2007-05-01·Molecular Pharmacology3区 · 医学

Vitamin D₃ Derivatives with Adamantane or Lactone Ring Side Chains are Cell Type-Selective Vitamin D Receptor Modulators

3区 · 医学

Article

作者: Matsunawa, Manabu ; Yoshimoto, Nobuko ; Uno, Shigeyuki ; Inaba, Yuka ; Makishima, Makoto ; Yamamoto, Keiko ; Yamada, Sachiko

The vitamin D receptor (VDR) mediates the biological actions of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the active form of vitamin D, which regulates calcium homeostasis, immunity, cellular differentiation, and other physiological processes. We investigated the effects of three 1,25(OH)(2)D(3) derivatives on VDR function. AD47 has an adamantane ring and LAC67a and LAC67b have lactone ring substituents at the side chain position. These vitamin D derivatives bind to VDR but do not stabilize an active cofactor conformation. In a VDR transfection assay, AD47 and LAC67b act as partial agonists and all three compounds inhibit VDR activation by 1,25(OH)(2)D(3). The derivatives enhanced the heterodimerization of VDR with the retinoid X receptor, an effect unrelated to agonist/antagonist activity. AD47 and LAC67b weakly induced recruitment of the SRC-1 cofactor to VDR, and all three derivatives inhibited the recruitment of p160 family cofactors to VDR induced by 1,25(OH)(2)D(3). It is noteworthy that AD47 induced DRIP205 recruitment as effectively as 1,25(OH)(2)D(3), whereas LAC67a and LAC67b were not effective. We examined the expression of endogenous VDR target genes and the nuclear protein levels of VDR and cofactors in several cell lines, including cells derived from intestine, bone, and monocytes, and found that the vitamin D(3) derivatives act as cell type-selective VDR modulators. The data indicate that side chain modification is useful in the development of VDR antagonists and tissue-selective modulators. Further elucidation of the molecular mechanisms of action of selective VDR modulators will be essential for their clinical application.

100 项与 AD-047 相关的药物交易

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