Citarinostat(Citarinostat) - 药物靶点：HDAC6_在研适应症：多发性骨髓瘤，阴燃多发性骨髓瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Citarinostat (USAN)

+ [2]

靶点

HDAC6

作用机制

HDAC6抑制剂(组蛋白去乙酰化酶-6抑制剂)

治疗领域

肿瘤免疫系统疾病心血管疾病+ [1]

在研适应症

多发性骨髓瘤阴燃多发性骨髓瘤

非在研适应症

晚期恶性实体瘤不可切除的黑色素瘤

原研机构

Acetylon Pharmaceuticals, Inc.

在研机构

OncoPep, Inc.

Acetylon Pharmaceuticals, Inc.

Celgene Corp.

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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结构

分子式C24H26ClN5O3

InChIKeyVLIUIBXPEDFJRF-UHFFFAOYSA-N

CAS号1316215-12-9

关联

5

项与 Citarinostat 相关的临床试验

NCT02886065 / Active, not recruiting临床1期IIT

A Phase 1b Study of PVX-410, a Multi-Peptide Cancer Vaccine, and Citarinostat (CC-96241), a Histone Deacetylase Inhibitor (HDAC) With and Without Lenalidomide for Patients With Smoldering Multiple Myeloma

This research study is studying a targeted therapy as a possible treatment for Smoldering Multiple Myeloma.
The following intervention will be involved in this study:
Lenalidomide
Citarinostat (CC-96241)
PVX-410

开始日期2017-03-07

申办/合作机构

The General Hospital Corp.

[+2]

NCT02935790 / Completed临床1期

A Phase 1b Study of the Selective HDAC6 Inhibitor ACY-241 in Combination With Ipilimumab and Nivolumab in Patients With Unresectable Stage III or Stage IV Melanoma

Determine the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of ACY-241 in combination with ipilimumab and nivolumab in patients with unresectable Stage III/Stage IV melanoma.

开始日期2016-09-30

申办/合作机构

Celgene Corp.

[+4]

NCT02635061 / Terminated临床1期

A Phase 1b Study of the Selective HDAC6 Inhibitor ACY-241 in Combination With Nivolumab in Patients With Unresectable Non-Small Cell Lung Cancer

Determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD) of ACY 241 in combination with nivolumab.

开始日期2016-08-25

申办/合作机构

Celgene Corp.

100 项与 Citarinostat 相关的临床结果

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100 项与 Citarinostat 相关的转化医学

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100 项与 Citarinostat 相关的专利（医药）

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24

项与 Citarinostat 相关的文献（医药）

2024-05-01·Leukemia

Correction to: Histone deacetylase (HDAC) inhibitor ACY241 enhances anti-tumor activities of antigen-specific central memory cytotoxic T lymphocytes against multiple myeloma and solid tumors

作者: Song, Yan ; Richardson, Paul ; Tai, Yu-Tzu ; Raje, Noopur ; Bae, Jooeun ; Hideshima, Teru ; Munshi, Nikhil C ; Anderson, Kenneth C

2024-01-01·The Korean Journal of Physiology & Pharmacology

ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial–mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha

Article

作者: Jeong, Chul-Ho ; Park, Seong-Jun ; Lee, Naeun

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

2023-09-19·Biochemistry

Structure and Function of Kdac1, a Class II Deacetylase from the Multidrug-Resistant Pathogen Acinetobacter baumannii

Article

作者: Watson, Paris R. ; Christianson, David W.

Proteomics studies indicate that 10% of proteins in the opportunistic pathogen Acinetobacter baumannii are acetylated, suggesting that lysine acetyltransferases and deacetylases function to maintain and regulate a robust bacterial acetylome. As the first step in exploring these fascinating prokaryotic enzymes, we now report the preparation and characterization of the lysine deacetylase Kdac1. We show that Kdac1 catalyzes the deacetylation of free acetyllysine and acetyllysine tetrapeptide assay substrates, and we also report the X-ray crystal structures of unliganded Kdac1 as well as its complex with the hydroxamate inhibitor Citarinostat. Kdac1 is a tetramer in solution and in the crystal; the crystal structure reveals that the L1 loop functions to stabilize quaternary structure, forming inter-subunit hydrogen bonds and salt bridges around a central arginine residue (R30). Surprisingly, the L1 loop partially blocks entry to the active site, but it is sufficiently flexible to allow for the binding of two Citarinostat molecules in the active site. The L12 loop is also important for maintaining quaternary structure; here, a conserved arginine (R278) accepts hydrogen bonds from the backbone carbonyl groups of residues in an adjacent monomer. Structural comparisons with two other prokaryotic lysine deacetylases reveal conserved residues in the L1 and L12 loops that similarly support tetramer assembly. These studies provide a structural foundation for understanding enzymes that regulate protein function in bacteria through reversible lysine acetylation, serving as a first step in the exploration of these enzymes as possible targets for the development of new antibiotics.

100 项与 Citarinostat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10918	-	-	DB15449

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
多发性骨髓瘤	临床2期	-	Acetylon Pharmaceuticals, Inc.	-
阴燃多发性骨髓瘤	临床1期	美国	Celgene Corp.	2017-03-07
阴燃多发性骨髓瘤	临床1期	美国	OncoPep, Inc.	2017-03-07
不可切除的黑色素瘤	药物发现	美国	Celgene Corp.	2016-09-30
晚期恶性实体瘤	药物发现	美国	Celgene Corp.	2015-12-22

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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


NCT02635061 (Pubmed \| Front Oncol)	临床1期	晚期非小细胞肺癌	18	ACY-241	(糧製窪窪範選夢鬱艱蓋) = 觸遞蓋壓製醖壓鹹簾獵鹹顧襯築繭築膚衊網鹽 (繭構窪憲壓顧遞鹽餘獵 )	-	2021-01-01
NCT02551185 (ASCO2018) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	20	paclitaxel+citarinostat	(憲構範夢餘蓋窪遞築艱) = citarinostat 360 mg/day 醖襯憲鏇構蓋鏇糧糧鬱 (壓鑰網餘選製夢選餘憲 ) 更多	积极	2018-06-04
NCT02400242 (ACE-MM-200, ASH2016) 人工标引	临床1期	多发性骨髓瘤	40	Pomalidomide+Dexamethasone+ACY-241	(鑰壓窪觸鹽選構醖艱淵) = 1 grade 4 thrombocytopenia at 360 mg 廠遞膚願夢齋廠壓顧顧 (網構鬱構顧鑰觸廠簾蓋 ) 更多	积极	2016-12-02