他喹莫德(Tasquinimod) - 药物靶点：HDAC4 x NIF_在研适应症：原发性血小板增多症后骨髓纤维化，真性红细胞增多症后骨髓纤维化，原发性骨髓纤维化_专利_临床

概要

基本信息

药物类型

小分子化药

别名

TASQ、ABR-215050、ABR-5050

靶点

HDAC4 x NIF

作用方式

抑制剂

作用机制

HDAC4抑制剂(组蛋白去乙酰化酶-4抑制剂)、NIF抑制剂(钙结合蛋白S100A9抑制剂)

治疗领域

血液及淋巴系统疾病其他疾病肿瘤+ [1]

在研适应症

原发性血小板增多症后骨髓纤维化真性红细胞增多症后骨髓纤维化原发性骨髓纤维化+ [2]

非在研适应症

前列腺腺癌去势抵抗性前列腺癌转移性去势抵抗性前列腺癌+ [6]

原研机构

Active Biotech AB

在研机构

Active Biotech ABHemato-Oncologie voor Volwassenen Nederland

非在研机构

Ipsen SA

Apoteket AB

博福--益普生（天津）制药有限公司

+ [1]

权益机构

Active Biotech AB

Ipsen SAUniversity of Pennsylvania Medical Center

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)暂停

特殊审评孤儿药 (美国)

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结构/序列

分子式C20H17F3N2O4

InChIKeyONDYALNGTUAJDX-UHFFFAOYSA-N

CAS号254964-60-8

关联

14

项与他喹莫德相关的临床试验

NCT06605586

/ Recruiting临床1/2期IIT

A Phase 1b/2 Trial with Tasquinimod in Patients with Myelofibrosis (primary, Post-PV or PostET) Refractory to or Intolerant for JAK2 Inhibition: the TasqForce Trial

The goal of this clinical trial is to learn if therapy can be improved in patients with myelofibrosis (MF) who have primary resistance or who have progressed after treatment with a Janus kinase (JAK) inhibitor or are intolerant for this category of drugs.
The main questions it aims to answer are:
* To evaluate the feasibility and safety of once daily dose of tasquinimod for 24 weeks (6 cycles)
* To determine the optimal dose
Patients will be treated once daily with tasquinimod for a maximum period of 24 weeks (6 cycles).
During the study most (diagnostic) procedures are part of the standard of care. Different from standard of care:
* Participation may lead to extra visits to the outpatient clinic
* Additional blood will be drawn when blood is already taken per standard of care
* Bone marrow sampling at entry and at the end of the trial
* MRI scans (or CT-scans) have to be performed
* Quality-of-life questionnaires have to be filled out

开始日期2025-02-20

申办/合作机构

Hemato-Oncologie voor Volwassenen Nederland

NCT06327100

/ Recruiting临床2期IIT

Open Label Phase 2 Study of Tasquinimod in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)

To learn if tasquinimod either alone or in combination with ruxolitinib can help to control PMF, post-PV MF, or post-ET MF.

开始日期2024-08-01

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

ACTRN12621000016831

/ Not yet recruiting临床2期

A randomized, double-blind, placebo-controlled phase II trial to evaluate the efficacy of tasquinimod in reducing the time taken for a 2-point decrease in admission status.in adults with COVID-19

开始日期2022-12-15

申办/合作机构

Hunter Medical Research Institute

100 项与他喹莫德相关的临床结果

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100 项与他喹莫德相关的转化医学

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100 项与他喹莫德相关的专利（医药）

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110

项与他喹莫德相关的文献（医药）

2025-03-01·CELLULAR SIGNALLING

Aerobic plus resistance exercise attenuates skeletal muscle atrophy induced by dexamethasone through the HDAC4/FoxO3a pathway

Article

作者: Wang, Danni ; Tian, Jiatong ; Ma, Jianxiong ; Liu, Sujuan ; Liang, Dehuan ; Xiang, Heng ; Niu, Yanmei ; Zheng, Xinyue ; Yu, Chunxia

This study aimed to investigate the underlying mechanisms by which physical exercise mitigates muscle atrophy induced by Dexamethasone (Dex). A muscle atrophy model was established in the mouse C2C12 cell line and 8-week-old mice treated with Dex, with subsequent verification of phenotype and atrogene expression. The potential benefits of combined aerobic and resistance exercise in mitigating muscle atrophy were then examined. To elucidate the involvement of Histone deacetylase 4 (HDAC4) in the protective effects of exercise against muscle loss, a combination of RT-PCR, Western blotting, immunoprecipitation, and immunofluorescence staining techniques were employed. The upregulation of HDAC4 was observed following Dex-induced muscle atrophy in vitro and in vivo. Inhibition of HDAC4 in C2C12 cells resulted in an increase in myotube diameter and fusion index, along with a decrease in the expression of Atrogin-1 and MuRF1. Treatment with Tasquinimod, an HDAC4 inhibitor, effectively prevented muscle wasting and dysfunction in mice induced by Dex. After a 6-week exercise intervention, the Dex-Exercise group exhibited significant improvements in body fat level, hyperinsulinemia, muscle mass and function in comparison to the Dex-Sedentary group. Mechanistically, we discovered that HDAC4 bound to and deacetylated Forkhead box protein O 3a (FoxO3a) within the nucleus, leading to decreased phosphorylation of FoxO3a at Ser 253. This interaction subsequently facilitated the expression of downstream atrogene Atrogin-1 and MuRF1, resulting in muscle atrophy. Conversely, exercise was found to potentially mitigate muscle atrophy by inhibiting the HDAC4/FoxO3a pathway. These findings suggest that HDAC4 may be a potential therapeutic target for exercise to combat Dex-induced muscle atrophy.

2025-03-01·KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY

Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway

Article

作者: Min, Xiao-Jia ; Lin, Ying ; Wu, Ya-Hong ; Li, Zhao ; Guo, Ye-Qing

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms. RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

2024-06-01·Bioactive materials

Enhanced osteochondral regeneration with a 3D-Printed biomimetic scaffold featuring a calcified interfacial layer

Article

作者: Yu, Mingzhao ; Zhang, Changqing ; Yin, Wenjing ; Wu, Di ; Hu, Bin ; Deng, Jue ; Yu, Qingxiao ; Zheng, Kaiwen ; Wei, Xiaojuan

The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic-chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/β-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.

22

项与他喹莫德相关的新闻（医药）

2025-05-23

·activebiotech.com

Active Biotech reports study results with tasquinimod in heavily pre-treated patients with relapsed refractory multiple myeloma

“These results confirm the feasibility of combining tasquinimod in an all-oral combination with standard-of-care agents for patients with multiple myeloma who have exhausted other treatment options,” said Dr. Dan Vogl, Principal Investigator. In this analysis, a total of 17 patients received tasquinimod in combination with IRd. During dose-escalation, no dose-limiting toxicities were observed, and dose level two (tasquinimod 1 mg daily after a one week run-in at 0.5 mg daily) was selected as the dose for the expansion cohort. Patients were heavily pretreated with a median of 7 prior lines of therapy (range 4-19) and all were triple-class refractory with 71% (12 pts) refractory to their most recent Imid/PI combination. Among these 12 patients, there was one durable Partial Response (PR) and three Minimal Responses (MR). These data are in line with previously reported results confirming the safety, tolerability and anti-myeloma effect of tasquinimod alone and in combination with IRd in patients with relapsed refractory multiple myeloma. ”Importantly, the observed responses in patients with myeloma previously refractory to an Imid/PI combination, who would not be expected to respond to the IRd backbone regimen, suggest synergistic efficacy of tasquinimod with IRd. These results highlight the potential for targeting the tumor microenvironment as a way to augment the efficacy of other myeloma therapies,” said Dr. Vogl. The study (NCT04405167), which is conducted at Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, has closed to enrolment, and the full study results are being analyzed. The abstract is available online on https://meetings.asco.org/ after 5 PM (ET) on May 22. Details on the presentation: Abstract Title: Clinical Activity of Novel Targeting of S100A9 with Tasquinimod for Relapsed and Refractory Multiple Myeloma (RRMM) Session Title: Hematologic Malignancies – Plasma Cell Dyscrasia Abstract Number: 7555 Session Date and Time: June 1, 2025, 8:00 AM-12:00 AM (ET)

临床结果临床研究

2025-05-21

·activebiotech.com

Active Biotech announces patent for tasquinimod in myelofibrosis granted in Europe

“We are very pleased that this significant patent has been granted by the EPO. It is an important step in the development program for tasquinimod in hematological malignancies, with a primary focus on myelofibrosis,” said Active Biotech’s CEO Helén Tuvesson. The patent, with the European patent number, 4185292 provides protection and market exclusivity in strategic European markets through 2041 for the use of tasquinimod in treatment of myeloproliferative neoplasms (MPN) i.e. myelofibrosis. The patent, issued in the name of Erasmus University Medical Center (Erasmus MC), Rotterdam was licensed exclusively to Active Biotech from Oncode Institute, acting on behalf of Erasmus MC, in 2022.

专利到期

2025-05-08

·activebiotech.com

Active Biotech Interim Report Q1 2025

FIRST QUARTER IN BRIEF US Patent Office granted Active Biotech’s patent application for laquinimod in eye disorders (January 28) Active Biotech announced that the first patient was enrolled in the European clinical study of tasquinimod in myelofibrosis (February 24) Active Biotech announced that the first patient was dosed in the phase II study of tasquinimod in myelofibrosis in the US (March 10) EVENTS AFTER THE END OF THE PERIOD Active Biotech reported positive top-line results from the LION study on ocular absorption and distribution of laquinimod in the eye (May 5) FINANCIAL SUMMARY The report is also available at www.activebiotech.com The information was submitted, through the agency of the contact person below, for public disclosure on 2025-05-08 at 08:30 CEST. Active Biotech AB (Corp. reg. no. 556223-9227) / Scheelevägen 22, SE-223 63 Lund / +46 46 19 20 00

临床结果临床2期财报

100 项与他喹莫德相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	他喹莫德	-	DB05861

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
去势抵抗性前列腺癌	临床3期	中国	Ipsen SA	2014-01-01
前列腺腺癌	临床3期	美国	Active Biotech AB	2011-03-24
前列腺腺癌	临床3期	美国	Apoteket AB	2011-03-24
前列腺腺癌	临床3期	阿根廷	Apoteket AB	2011-03-24
前列腺腺癌	临床3期	阿根廷	Active Biotech AB	2011-03-24
前列腺腺癌	临床3期	澳大利亚	Active Biotech AB	2011-03-24
前列腺腺癌	临床3期	澳大利亚	Apoteket AB	2011-03-24
前列腺腺癌	临床3期	比利时	Active Biotech AB	2011-03-24
前列腺腺癌	临床3期	比利时	Apoteket AB	2011-03-24
前列腺腺癌	临床3期	巴西	Apoteket AB	2011-03-24

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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


NCT04405167 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	复发性多发性骨髓瘤	10	tasquinimod	觸築淵糧積鏇獵製鏇襯(憲鹽壓窪顧憲積鹹蓋餘) = 0.5 mg qd x1 wk, then 1 mg qd (a single-agent MTD of 1 mg daily after a 1-week dose escalation) 夢醖淵簾膚積糧願鑰鹹 (鹽膚憲範築鬱網構膚築 ) 更多	积极	2023-05-26
NCT02057666 (TasQ003, CTgov)	临床3期	去势抵抗性前列腺癌 \| 转移性去势抵抗性前列腺癌	146	Tasquinimod (Tasquinimod)	願鑰遞襯蓋憲窪鑰網齋(選簾淵夢製鑰觸鬱鹽艱) = 鬱積廠蓋窪廠夢餘壓廠繭壓選憲積餘範壓淵淵 (蓋淵醖鹹選壓積襯獵簾, 窪獵醖選糧鏇觸築膚網 ~ 鏇膚蓋鬱廠鏇膚鏇網積) 更多	-	2021-04-23
				Placebo (Placebo)	願鑰遞襯蓋憲窪鑰網齋(選簾淵夢製鑰觸鬱鹽艱) = 衊壓糧襯憲鬱選衊膚膚繭壓選憲積餘範壓淵淵 (蓋淵醖鹹選壓積襯獵簾, 廠齋壓網膚鑰艱觸憲選 ~ 積遞壓獵糧淵憲選憲遞) 更多
NCT01743469 (CTgov)	临床2期	转移性肾细胞癌 \| 卵巢癌 \| 肿瘤转移 ... 更多	201	Tasquinimod (Hepatocellular Carcinoma Cohort)	壓選獵願遞膚窪獵夢範 = 選製餘鏇簾廠積壓鏇網構憲憲艱範鏇製齋夢窪 (淵簾襯夢簾膚糧製糧窪, 鹽壓艱廠鬱鹽構範願積 ~ 艱鑰簾繭鏇網憲齋構鑰) 更多	-	2018-05-07
				Tasquinimod (Ovarian Carcinoma Cohort)	壓選獵願遞膚窪獵夢範 = 繭衊願齋顧簾積醖範襯構憲憲艱範鏇製齋夢窪 (淵簾襯夢簾膚糧製糧窪, 壓網鬱構衊繭鏇膚網遞 ~ 襯製顧餘顧製廠鏇餘遞) 更多
NCT01732549 (Pubmed \| Ann Oncol) 人工标引	临床2期	转移性去势抵抗性前列腺癌一线	144	tasquinimod	壓衊齋鬱鬱壓觸襯積艱(蓋簾膚窪蓋淵製鹹遞鏇) = 壓窪憲膚壓製窪蓋鬱鑰選憲夢選餘窪壓餘繭選 (製齋範鏇構鏇鏇遞鏇範, 24.3 ~ 53.7) 更多	积极	2017-11-01
				Placebo	壓衊齋鬱鬱壓觸襯積艱(蓋簾膚窪蓋淵製鹹遞鏇) = 淵築淵鏇範齋製鬱蓋膚選憲夢選餘窪壓餘繭選 (製齋範鏇構鏇鏇遞鏇範, 16.1 ~ 25.9) 更多
NCT01732549 (Pubmed)	临床2期	转移性去势抵抗性前列腺癌维持	144	Tasquinimod	範製鏇鏇衊範築夢蓋鏇(鬱遞壓鬱鹹顧積獵憲糧) = 膚願膚鹹鑰餘醖鬱憲獵廠餘鑰範憲齋憲鏇獵糧 (願遞簾觸網願獵醖糧鏇, 24.3 ~ 53.7)	积极	2017-11-01
				Placebo	範製鏇鏇衊範築夢蓋鏇(鬱遞壓鬱鹹顧積獵憲糧) = 鏇餘鏇顧簾積願觸構窪廠餘鑰範憲齋憲鏇獵糧 (願遞簾觸網願獵醖糧鏇, 16.1 ~ 25.9)
NCT01743469 (Pubmed \| Target Oncol)	临床2期	胃癌	201	Tasquinimod (Hepatocellular cancer)	蓋憲網願鑰壓觸觸網窪(淵憲願觸蓋願鑰築網衊) = 壓襯鬱鹹選淵夢鹹積網蓋憲壓膚觸遞築壓淵壓 (膚蓋鏇淵鏇醖醖顧簾壓 )	不佳	2017-10-01
				Tasquinimod (Ovarian cancer)	蓋憲網願鑰壓觸觸網窪(淵憲願觸蓋願鑰築網衊) = 簾淵鏇廠積夢壓簾網遞蓋憲壓膚觸遞築壓淵壓 (膚蓋鏇淵鏇醖醖顧簾壓 )
NCT01732549 (CTgov)	临床2期	去势抵抗性前列腺癌	144	Tasquinimod (Tasquinimod)	構醖顧願積齋範廠選醖(淵壓鏇鬱範鹹廠醖夢獵) = 繭壓醖積範夢憲壓蓋觸鹽廠艱鑰選網網網鏇選 (醖獵範積積憲廠觸醖餘, 積選積餘憲顧夢願鹹餘 ~ 製餘淵遞衊構鏇艱糧襯) 更多	-	2016-10-03
				Placebo (Placebo)	構醖顧願積齋範廠選醖(淵壓鏇鬱範鹹廠醖夢獵) = 遞夢鏇艱鏇壓鏇觸襯艱鹽廠艱鑰選網網網鏇選 (醖獵範積積憲廠觸醖餘, 鬱構獵遞選糧選鬱構淵 ~ 憲遞壓糧願繭鹹襯範積) 更多
NCT01234311 (Pubmed \| J Clin Oncol)	临床3期	转移性去势抵抗性前列腺癌	-	Tasquinimod	憲襯鏇蓋範夢醖廠鑰窪(築艱鑰醖顧遞鏇餘窪鬱) = 繭獵壓積壓糧築蓋築餘積艱築淵繭淵顧廠醖網 (範壓顧餘醖繭廠蓋夢網, 19.5 ~ 23.0) 更多	积极	2016-08-01
				Placebo	憲襯鏇蓋範夢醖廠鑰窪(築艱鑰醖顧遞鏇餘窪鬱) = 製餘窪窪繭餘遞襯齋顧積艱築淵繭淵顧廠醖網 (範壓顧餘醖繭廠蓋夢網, 21.4 ~ 26.9) 更多
NCT02159950 (CTgov)	临床2期	复发性前列腺癌 \| 去势抵抗性前列腺癌 \| 转移性去势抵抗性前列腺癌 ... 更多	2	Laboratory Biomarker Analysis+Sipuleucel-T (Arm I (Sipuleucel-T))	蓋糧鏇艱壓顧範鹽願餘(範衊醖簾鏇選齋繭糧願) = 顧醖鹽鹽憲窪糧廠夢網簾繭觸繭鑰鬱築遞選醖 (齋壓糧獵繭構鏇獵繭簾, 餘製鑰範醖廠膚糧壓廠 ~ 膚餘窪積淵製廠繭遞築) 更多	-	2016-05-20
				Laboratory Biomarker Analysis+Tasquinimod+Sipuleucel-T (Arm II (Tasquinimod, Sipuleucel-T))	繭餘顧衊膚醖糧膚選醖 = 夢選鬱糧築簾膚鹽蓋製淵簾餘顧繭餘獵艱顧憲 (餘築膚壓鹹廠憲齋獵獵, 窪簾鹹鏇蓋鏇網遞壓壓 ~ 衊廠網鏇襯窪蓋範積鏇) 更多
NCT00560482 (ASCO2013)	临床2期	转移性去势抵抗性前列腺癌	201	Tasquinimod	衊壓夢鹽窪觸築鏇觸積(餘製廠艱製糧窪網簾築) = 遞鬱簾選餘襯構獵願淵餘艱齋選鑰獵齋積鬱鏇 (餘鏇遞構築簾鬱蓋築餘 )	-	2013-05-20