Quisinostat Hydrochloride(Quisinostat Hydrochloride) - 药物靶点：HDAC1_在研适应症：葡萄膜黑色素瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Quisinostat、Quisinostat hydrochloride (USAN)

+ [1]

靶点

HDAC1

作用方式

抑制剂

作用机制

HDAC1抑制剂(组蛋白去乙酰化酶-1抑制剂)

治疗领域

肿瘤眼部疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

葡萄膜黑色素瘤

非在研适应症

晚期恶性实体瘤皮肤T细胞淋巴瘤输卵管癌+ [7]

原研机构

Janssen Global Services LLC

在研机构

Viriom, Inc.

非在研机构

Janssen Pharmaceutica NVJanssen Research & Development LLCNewVac LLC

+ [1]

权益机构

Janssen Pharmaceuticals, Inc.NewVac LLC

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C21H27ClN6O2

InChIKeyTWNOICNTTFKOHQ-UHFFFAOYSA-N

CAS号1083078-98-1

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关联

8

项与 Quisinostat Hydrochloride 相关的临床试验

NCT06932757

/ Not yet recruiting临床2期IIT

Phase 2 Trial of Adjuvant Quisinostat in High-Risk Uveal Melanoma

The purpose of this study is to see if giving participants quisinostat will prevent participants' uveal melanoma tumor from spreading. The researchers want to find out the effects that quisinostat has on participants' condition.

开始日期2025-06-01

申办/合作机构

University of Miami

[+1]

NCT06824662

/ Not yet recruiting早期临床1期IIT

A Phase 0/1b 'Trigger' Clinical Trial With an Expansion Phase of Quisinostat Plus Fractionated Radiotherapy in Newly-diagnosed and Recurrent Grade 4 IDH-WT Glioblastomas

This is an open-label, multi-center Phase 0/1b study that will enroll up to 18 participants with recurrent WHO grade 4 glioblastoma (rGBM) IDH-wildtype (IDH-WT), Arm A, and 12 participants with presumed newly-diagnosed WHO grade 4 glioblastoma (nGBM) IDH-WT, Arm B. The trial will be composed of a Phase 0 component (subdivided into Arms A and B), and an Expansion Phase 1b. Patients with tumors demonstrating a positive pharmacokinetic (PK) response in the Phase 0 component of the study will graduate to an Expansion Phase that combines therapeutic dosing of quisinostat plus standard-of-care fractionated radiotherapy (RT).

开始日期2025-05-01

申办/合作机构

St. Joseph's Medical Center, Inc.

NCT02948075

/ Completed临床2期

Multicenter, Open-label Study of Safety and Efficacy of Quisinostat in Combination With Paclitaxel + Carboplatin Chemotherapy in Patients With Metastatic or Locally Advanced Epithelial Ovarian Cancer, Primarily Peritoneal or Fallopian Tube Carcinoma, Resistant to First Line Platinum and Paclitaxel Based Chemotherapy

This is a multicenter, open-label study of safety and efficacy of Quisinostat in combination with Paclitaxel + Carboplatin chemotherapy in patients with metastatic or locally advanced epithelial ovarian cancer, primarily peritoneal or fallopian tube carcinoma, resistant to first line platinum and Paclitaxel based chemotherapy.
The study will be carried out in 5-8 Russian and Belarusian sites. A maximum of 32 patients with metastatic or locally advanced epithelial ovarian cancer, primarily peritoneal or fallopian tube carcinoma, resistant to first line platinum and Paclitaxel based chemotherapy, will be enrolled in the study.

开始日期2015-09-01

申办/合作机构

NewVac LLC

[+1]

100 项与 Quisinostat Hydrochloride 相关的临床结果

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100 项与 Quisinostat Hydrochloride 相关的转化医学

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100 项与 Quisinostat Hydrochloride 相关的专利（医药）

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178

项与 Quisinostat Hydrochloride 相关的文献（医药）

2025-04-01·HemaSphere

H1‐0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia

Article

作者: Schaal, Katerina ; Suppiyar, Vithusan ; Bhave, Rigveda ; Wang, Herui ; Borkhardt, Arndt ; Hanel, Andrea ; Fischer, Ute ; Hasselmann, Rebecca ; Schliehe‐Diecks, Julian ; Kath, Carla‐Johanna ; Bhatia, Sanil ; Koppstein, David ; Remke, Marc ; Kameri, Ersen ; Prasad, Yash ; Picard, Daniel ; Mehtonen, Juha ; Kögler, Gesine ; Hein, Daniel ; Heinäniemi, Merja ; Lautwein, Tobias ; Tu, Jia‐Wey ; Zhuang, Zhengping ; Rüchel, Nadine ; Jepsen, Vera H. ; Wagener, Rabea ; Blümel, Lena ; Qin, Nan

AbstractETV6::RUNX1, the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP‐ALL), induces a clinically silent preleukemic state that can persist in carriers for over a decade and may progress to overt leukemia upon acquisition of secondary lesions. The mechanisms contributing to quiescence of ETV6::RUNX1+ preleukemic cells still remain elusive. In this study, we identify linker histone H1‐0 as a critical mediator of the ETV6::RUNX1+ preleukemic state by employing human ‐induced pluripotent stem cell (hiPSC) models engineered by using CRISPR/Cas9 gene editing. Global gene expression analysis revealed upregulation of H1‐0 in ETV6::RUNX1+ hiPSCs that was preserved upon hematopoietic differentiation. Moreover, whole transcriptome data of 1,727 leukemia patient samples showed significantly elevated H1‐0 levels in ETV6::RUNX1+ BCP‐ALL compared to other leukemia entities. Using dual‐luciferase promoter assays, we show that ETV6::RUNX1 induces H1‐0 promoter activity. We further demonstrate that depletion of H1‐0 specifically inhibits ETV6::RUNX1 signature genes, including RAG1 and EPOR. Single‐cell sequencing showed that H1‐0 is highly expressed in quiescent hematopoietic cells. Importantly, H1‐0 protein levels correspond to susceptibility of BCP‐ALL cells towards histone deacetylase inhibitors (HDACis) and combinatorial treatment using the H1‐0‐inducing HDACi Quisinostat showed promising synergism with established chemotherapeutic drugs. Taken together, our data identify H1‐0 as a key regulator of the ETV6::RUNX1+ transcriptome and indicate that the addition of Quisinostat may be beneficial to target non‐responsive or relapsing ETV6::RUNX1+ BCP‐ALL.

2025-03-07·Neuro-Oncology

TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas

Article

作者: Zhang, Tao ; Dai, Yuting ; Liu, Fang ; Huang, Ning ; Li, Chuanbao ; Wu, Zhe Bao ; Liu, Yanting ; Tang, Hao ; Wang, Xiaobin ; Xue, Li ; Han, Tianyi ; Lin, Shaojian

AbstractBackgroundPituitary adenomas (PAs) are common intracranial tumors and the TRIM family plays a crucial role in cell proliferation and therapeutic resistance of tumors. However, the role of the TRIM family in PAs is not well recognized.MethodsCRISPR screening explored the role of the TRIM family in cell proliferation and drug resistance in PAs. In vitro and in vivo experiments were performed to evaluate the effects of Tripartite Motif Containing 21 (TRIM21). RNA-sequencing, mass spectrometry, immunoprecipitation, and ubiquitination experiments were performed to explore the molecular mechanism. NanoBiT assays were used to screen the drugs reducing TRIM21 expression.ResultsCRISPR-Cas9 screens identified that TRIM21 facilitated cell proliferation and drug resistance in PAs. Mechanistically, TRIM21 interacted with ERK1/2 through PRY-SPRY domain, leading to ERK1/2 K27-linked ubiquitination. The ERK1/2 ubiquitination promotes the interaction between ERK1/2 and MEK1/2, thereby facilitating the phosphorylation of ERK1/2. However, an excess presence of TRIM21 suppressed the phosphorylation of ERK1/2 and cell proliferation via activating ERK1/2 negative feedback pathways. Importantly, TRIM21 was upregulated in dopamine-resistant prolactinomas and cabergoline-resistant MMQ cells. Furthermore, drug screening identified that Fimepinostat and Quisinostat, can reduce the protein levels of TRIM21, inhibit tumor progression, and increase drug sensitivity.ConclusionsTRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.

2025-03-01·Virology

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry

Article

作者: Tietjen, Ian ; Liang, Kimberly ; Cassel, Joel ; Ntie-Kang, Fidele ; Montaner, Luis J ; Salvino, Joseph M ; Nkwelle, Chantal Emade ; Stephens, Unique ; Ndip, Roland N ; Esemu, Seraphine N

J-Lat cells are derivatives of the Jurkat CD4⁺ T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs). We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. For example, 10 μM prostratin induced a 20.1 ± 3.3-fold increase in GFP fluorescence in the microplate reader assay, which corresponded to 64.2 ± 5.0% GFP-positive cells detected by flow cytometery. Similarly, 0.3 μM prostratin induced a 1.7 ± 1.2-fold increase compared to 8.7 ± 5.7% GFP-positive cells detected. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts.

100 项与 Quisinostat Hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10322	Quisinostat Hydrochloride	-	DB12985

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
葡萄膜黑色素瘤	临床2期	美国	Viriom, Inc.	2025-06-01
输卵管癌	药物发现	俄罗斯	NewVac LLC	2015-09-01
皮肤T细胞淋巴瘤	药物发现	西班牙	Janssen Research & Development LLC	2011-11-01
皮肤T细胞淋巴瘤	药物发现	英国	Janssen Research & Development LLC	2011-11-01
皮肤T细胞淋巴瘤	药物发现	葡萄牙	Janssen Research & Development LLC	2011-11-01
皮肤T细胞淋巴瘤	药物发现	法国	Janssen Research & Development LLC	2011-11-01
皮肤T细胞淋巴瘤	药物发现	美国	Janssen Research & Development LLC	2011-11-01
皮肤T细胞淋巴瘤	药物发现	德国	Janssen Research & Development LLC	2011-11-01
晚期恶性实体瘤	药物发现	英国	Janssen Pharmaceutica NV	2007-08-01
晚期恶性实体瘤	药物发现	英国	Johnson & Johnson Pharmaceutical Research & Development LLC	2007-08-01

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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


NCT02948075 (ASCO2017)	临床2期	复发性铂耐药性输卵管癌	31	Quisinostat + Paclitaxel + Carboplatin	(築膚餘網糧鑰襯繭簾衊) = 襯繭糧蓋製蓋積醖顧餘淵膚願窪餘鏇廠鏇鬱鏇 (網蓋願鏇憲積獵廠網鏇 ) 更多	积极	2017-05-30
Pubmed \| Leuk Lymphoma	临床1期	复发性多发性骨髓瘤	-	Quisinostat	選醖網鬱鹽醖夢顧鑰範(窪糧選製鏇廠積簾衊製) = n = 11 蓋衊鹹遞鹹繭艱遞艱淵 (製鏇鑰鑰醖鏇築淵顧築 ) 更多	-	2016-07-02
NCT01464112 (ASCO2013)	临床1期	复发性多发性骨髓瘤	18	Quisinostat	(簾鏇願夢選襯衊鹹窪窪) = 襯壓構糧艱蓋糧蓋願構糧遞窪願艱鬱齋鬱簾積 (製製淵艱製選襯壓鬱鬱 ) 更多	-	2013-05-20
NCT01486277 (ASH 12012 \| ASH 22012) 人工标引	临床2期	皮肤T细胞淋巴瘤	26	quisinostat	(遞艱餘鑰網繭鑰夢鏇築) = 鏇網衊醖獵襯製鹽願齋醖獵膚艱夢鏇襯構觸廠 (衊範鑰鹹遞壓構夢壓夢 ) 更多	积极	2012-11-16
ASCO2011	临床1期	晚期癌症	73	JNJ-26481585 4 days on, 3 days off	(廠艱壓糧鹽鬱觸獵鹹遞) = 醖醖獵衊構衊夢築構糧築選憲遞遞積鹹壓衊網 (鏇願遞齋憲壓廠糧顧積 ) 更多	-	2011-05-20