他米巴罗汀(Tamibarotene) - 药物靶点：RARα_在研适应症：急性早幼粒细胞白血病，RARα阳性骨髓增生异常综合征，常染色体显性多囊肾病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Amnolake、Retinobenzoic acid、Tamibaro

+ [19]

靶点

RARα

作用机制

RARα激动剂(维甲酸受体α激动剂)

治疗领域

肿瘤血液及淋巴系统疾病其他疾病+ [2]

在研适应症

急性早幼粒细胞白血病RARα阳性骨髓增生异常综合征常染色体显性多囊肾病+ [1]

非在研适应症

晚期肝细胞癌晚期非小细胞肺癌乳腺癌+ [7]

原研机构

Nippon Shinyaku Co., Ltd.

在研机构

Syros Pharmaceuticals, Inc.

Rege Nephro Co. Ltd.初创企业Toko Pharmaceutical Industrial Co. Ltd.

非在研机构

LadRx Corp.R&R, Inc.

Zeria Pharmaceutical Co., Ltd.

最高研发阶段批准上市

首次获批日期

日本 (2005-04-11),

急性早幼粒细胞白血病

最高研发阶段(中国)-

特殊审评快速通道 (美国)、孤儿药 (美国)、孤儿药 (欧盟)

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结构

分子式C22H25NO3

InChIKeyMUTNCGKQJGXKEM-UHFFFAOYSA-N

CAS号94497-51-5

关联

31

项与他米巴罗汀相关的临床试验

NCT06289998 / Recruiting临床2期

Phase IIa Clinical Trial of Tamibarotene in Patients With Autosomal Dominant Polycystic Kidney Disease

Clinical trial of tamibarotene in patients with Autosomal Dominant Polycystic Kidney Disease

开始日期2023-12-22

申办/合作机构

Rege Nephro Co. Ltd.初创企业

JPRN-jRCT2011230055 / Suspended临床2期IIT

Phase IIa clinical trial of tamibarotene in patients with Autosomal Dominant Polycystic Kidney Disease

开始日期2023-12-12

申办/合作机构-

NCT06085638 / Withdrawn临床1/2期IIT

Phase I/II Study of SY-1425 (Tamibarotene) in Combination With Azacitidine and Venetoclax for Patients With Chronic Myelomonocytic Leukemia

To learn if adding venetoclax to the chemotherapy combination of tamibarotene and azacitidine is more effective than tamibarotene and azacitidine alone in treating higher-risk CMM

开始日期2023-09-14

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与他米巴罗汀相关的临床结果

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100 项与他米巴罗汀相关的转化医学

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100 项与他米巴罗汀相关的专利（医药）

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265

项与他米巴罗汀相关的文献（医药）

2024-08-01·CLINICAL IMMUNOLOGY

Integrated multi-omics analysis and machine learning developed diagnostic markers and prognostic model based on Efferocytosis-associated signatures for septic cardiomyopathy

Article

作者: Lin, Jibin ; Wang, Boyuan ; Li, Xuelian ; Wei, Yumiao ; Guo, Xiaopeng ; Jiang, Shijiu ; He, Shaolin

Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We used integrated multi-omics analysis to explore the clinical and genetic roles of efferocytosis in SCM. We identified six module genes (ATP11C, CD36, CEBPB, MAPK3, MAPKAPK2, PECAM1) strongly associated with SCM, leading to an accurate predictive model. Subgroups defined by EFFscore exhibited distinct clinical features and immune infiltration levels. Survival analysis showed that the C1 subtype with a lower EFFscore had better survival outcomes. scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from sepsis patients identified four genes (CEBPB, CD36, PECAM1, MAPKAPK2) associated with high EFFscores, highlighting their role in SCM. Molecular docking confirmed interactions between diagnostic genes and tamibarotene. Experimental validation supported our computational results. In conclusion, our study identifies a novel efferocytosis-related SCM subtype and diagnostic biomarkers, offering new insights for clinical diagnosis and therapy.

2024-07-22·BRITISH JOURNAL OF CANCER

Synthetic retinoid-mediated preconditioning of cancer-associated fibroblasts and macrophages improves cancer response to immune checkpoint blockade

Article

作者: Sassa, Naoto ; Tsukamoto, Tetsuya ; Ando, Ryota ; Hinohara, Kunihiko ; Kawashima, Hiroki ; Takahashi, Masahide ; Murakami, Takashi ; Sano, Tomoyasu ; Enomoto, Atsushi ; Akamatsu, Shusuke ; Mizutani, Yasuyuki ; Owaki, Takayuki ; Miyai, Yuki ; Akashi, Tomohiro ; Ishii, Makoto ; Hase, Tetsunari ; Yamamoto, Masami ; Shiraki, Yukihiro ; Matsukawa, Yoshihisa ; Mii, Shinji ; Esaki, Nobutoshi ; Nomura, Sachiyo ; Maeda, Motohiro ; Ishikawa, Takuya ; Yuguchi, Yuri ; Kato, Katsuhiro ; Iida, Tadashi

Abstract:

Background:

The proliferation of cancer-associated fibroblasts (CAFs) hampers drug delivery and anti-tumor immunity, inducing tumor resistance to immune checkpoint blockade (ICB) therapy. However, it has remained a challenge to develop therapeutics that specifically target or modulate CAFs.

Methods:

We investigated the involvement of Meflin+ cancer-restraining CAFs (rCAFs) in ICB efficacy in patients with clear cell renal cell carcinoma (ccRCC) and urothelial carcinoma (UC). We examined the effects of Am80 (a synthetic retinoid) administration on CAF phenotype, the tumor immune microenvironment, and ICB efficacy in cancer mouse models.

Results:

High infiltration of Meflin+ CAFs correlated with ICB efficacy in patients with ccRCC and UC. Meflin+ CAF induction by Am80 administration improved ICB efficacy in the mouse models of cancer. Am80 exerted this effect when administered prior to, but not concomitant with, ICB therapy in wild-type but not Meflin-deficient mice. Am80-mediated induction of Meflin+ CAFs was associated with increases in antibody delivery and M1-like tumor-associated macrophage (TAM) infiltration. Finally, we showed the role of Chemerin produced from CAFs after Am80 administration in the induction of M1-like TAMs.

Conclusion:

Our data suggested that Am80 administration prior to ICB therapy increases the number of Meflin+ rCAFs and ICB efficacy by inducing changes in TAM phenotype.

2024-06-28·MEDICINE

Identification of shared disease marker genes and underlying mechanisms between rheumatoid arthritis and Crohn disease through bioinformatics analysis

Article

作者: Shen, Ying ; Peng, Peifei

As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation. However, the underlying mechanisms and disease markers responsible for their cooccurrence remain unknown and have not been systematically studied. Therefore, this study aimed to identify key molecules and pathways commonly involved in both RA and CD through bioinformatic analysis of public sequencing databases. Datasets for RA and CD were downloaded from the GEO database. Overlapping genes were identified using weighted gene co-expression network analysis and differential analysis crossover, and enrichment analysis was conducted for these genes. Protein-protein interaction networks were then constructed using these overlapping genes to identify hub genes. Expression validation and receiver operating characteristic curve validation were performed for these hub genes using different datasets. Additionally, the immune cell correlation, single-cell expression cluster, and the immune cell expression cluster of the core gene were analyzed. Furthermore, upstream shared microRNAs (miRNA) were predicted and a miRNA-gene network was constructed. Finally, drug candidates were analyzed and predicted. These core genes were found to be positively correlated with multiple immune cells that are infiltrated by the disease. Analysis of gene expression clusters revealed that these genes were mostly associated with inflammatory and immune responses. The miRNA-genes network analysis suggested that hsa-miR-31-5p may play an important role in the common mechanism of RA and CD. Finally, tamibarotene, retinoic acid, and benzo[a]pyrene were identified as potential treatment options for patients with both RA and CD. This bioinformatics study has identified ITGB2, LCP2, and PLEK as key diagnostic genes in patients with both RA and CD. The study has further confirmed that inflammation and immune response play a central role in the development of both RA and CD. Interestingly, the study has highlighted hsa-miR-31-5p as a potential key player in the common mechanism of both diseases, representing a new direction in research and a potential therapeutic target. These shared genes, potential mechanisms, and regulatory networks offer new opportunities for further research and may provide hope for future treatment of patients with both RA and CD.

87

项与他米巴罗汀相关的新闻（医药）

2024-10-07

·PRNewswire

Rege Nephro Co., Ltd. Successfully Completes Series B Funding to Accelerate Kidney Disease Therapy Trials

KYOTO, Japan, Oct. 7, 2024 /PRNewswire/ -- Rege Nephro Co., Ltd. () is excited to announce that the company has successfully developed a funding plan of total 25 billion yen in new Series B funding and raised 22.5 billion yen with the first payment. This significant investment brings the company's total funding to 44 billion yen. The funding round attracted a mix of strategic investors, including DCI Partners Co., Ltd. as a lead investor, JIC Venture Growth Investments Co., Ltd., Nippon Venture Capital CO., Ltd., TOHOKU University Venture Partners Co., Ltd., Golden Asia Fund Ventures Ltd., Mitsui Chemicals, Inc., Global Brain Corporation, Kyoto University Innovation Capital Co., Ltd., JAFCO Group Co., Ltd., Mitsubishi UFJ Capital Co., Ltd., ASAHI KASEI CORPORATION, QB Capital, LLC who recognize the potential of Rege Nephro in delivering new treatments to patients suffering from their diseases. The newly acquired funds will be strategically used to advance the clinical trials of RN-014, our promising treatment in Phase II trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD), and to prepare for clinical trials in the United States. Additionally, the funding will support the completion of preclinical trials for our second innovative product, RN-032, aimed at treating Chronic Kidney Disease (CKD) through cell therapy. Investor Statements DCI Partners Co., Ltd. "We are excited to announce that we are the lead investor in this round of investment from our fund. We are fully committed to supporting the growth of Rege Nephro." JIC Venture Growth Investments Co., Ltd. "We strongly believe that his advanced drug discovery research based on Professor Osafune's discoveries will provide new therapeutic solutions for intractable renal diseases." Kyoto University Innovation Capital Co., Ltd. "We are delighted that Rege Nephro, which we have supported since before the company was founded, has finally entered the clinical stage. We hope that this funding will accelerate the clinical trials and bring a new therapeutic drug to patients as soon as possible." JAFCO Group Co., Ltd. "We hope that this financing will further accelerate Rege Nephro research and development in iPS drug discovery and provide new treatment options for patients suffering from diseases with limited treatment options." Mitsubishi UFJ Capital Co., Ltd. "Our continued investment reflects our confidence in Rege Nephro's rapid progress and the potential of Professor Osafune's iPS cell technology to significantly impact medical practice." Series B investors About Rege Nephro Co., Ltd. Rege Nephro Co., Ltd. is a clinical-stage biotech company utilizing induced pluripotent stem cell (iPSC)-based technology from the Center for iPS Cell Research and Application (CiRA), Kyoto University. It is developing therapeutics and cell therapy for kidney, liver, and pancreas diseases. About RN-014 Tamibarotene, under development for ADPKD, is a retinoic acid receptor (RAR) agonist expected to potently inhibit cyst formation and improve renal function. The Phase II clinical trial began in December 2023. This trial includes a pharmacokinetic (PK) phase and a randomization phase. Various safety measures have been established, including phased patient enrollment, periodic independent safety monitoring, strict criteria for dose reduction and discontinuation of the investigational drug, and criteria for discontinuation of the entire trial. There have been no significant issues at this time. About RN-032 Cell therapy using NPCs for Chronic Kidney Disease (CKD). Nephron progenitor cells (NPCs) are cells that give rise to nephrons. Rege Nephro has been tried implanting iNPCs (NPCs induced from allogeneic human iPSCs) into the damaged kidneys, and the improvements in renal function have been confirmed in the several mouse experiments. SOURCE Rege Nephro CO., Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

细胞疗法临床2期

2024-08-27

·Business Wire

Syros Pharmaceuticals to Present at Upcoming Medical and Investor Conferences

CAMBRIDGE, Mass.--( BUSINESS WIRE )--Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today announced that it will present additional data from the randomized portion of the SELECT-AML-1 Phase 2 clinical trial at the Society of Hematologic Oncology (SOHO) Annual Meeting taking place September 4-7, in Houston, Texas. Additionally, Syros announced that company management will participate in the H.C. Wainwright 26 th Annual Global Investment Conference, being held September 9-11 in New York City. Details are as follows: 12 th Annual Meeting of the Society of Hematologic Oncology (SOHO 2024) Presentation Title: SELECT-AML-1: Phase 2 Randomized Trial of Tamibarotene in Combination With Venetoclax and Azacitidine in Adult Patients With Previously Untreated AML With RARA Overexpression, Who Are Ineligible for Standard Induction Therapy Session Date & Time: Wednesday, September 4, 2024, 5:15-6:30 PM CT (6:15-7:30 PM ET) Location: George R. Brown Convention Center Poster Number: AML-347 The poster will be available on the Publications and Abstracts section of the Syros website at www.syros.com following the session. H.C. Wainwright 26 th Annual Global Investment Conference Presentation Date & Time: Monday, September 9, 2024, 11:30 AM ET Location: Lotte New York Palace A live webcast of the presentation will be available on the Investors & Media section of the Syros website at www.syros.com . An archived replay of the webcast will be available for approximately 30 days following the presentation. About Syros Pharmaceuticals Syros is committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. Driven by the motivation to help patients with blood disorders that have largely eluded other targeted approaches, Syros is developing tamibarotene, an oral selective RARα agonist in frontline patients with higher-risk myelodysplastic syndrome with RARA gene overexpression. For more information, visit www.syros.com and follow us on Twitter ( @SyrosPharma ) and LinkedIn .

临床2期ASH会议

2024-08-13

·Firstwordpharma

Syros ditches mid-stage tamibarotene programme in front-line AML

Shares in Syros Pharmaceuticals plunged as much as 70% in after-hours trading on Monday after the company announced plans to halt further enrolment in a Phase II study of tamibarotene for front-line acute myeloid leukaemia (AML) patients with RARA gene overexpression. “We are disappointed by this unexpected outcome,” remarked chief medical officer David Roth.The SELECT-AML-1 trial was investigating the oral retinoic acid receptor alpha (RARα) agonist in combination with venetoclax and azacitidine. Syros said that a prespecified analysis of 40 participants from a total of 51 newly diagnosed, unfit patients with AML, showed a complete response (CR)/complete response with incomplete haematologic recovery (CRi) rate of 65% for the tamibarotene-based triplet regimen compared with 70% for the venetoclax-azacitidine doublet regimen. The company noted that the “similar” results for the two arms suggest a low likelihood of the triplet regimen demonstrating superiority in the final analysis. Meanwhile, no new safety signals associated with the triplet were identified.MDS work continuesRoth noted that tamibarotene plus azacitidine demonstrated a 61% CR/CRi rate in newly diagnosed patients with AML in an earlier Phase II study, reinforcing the company’s “conviction” in pursuing a doublet strategy in higher-risk myelodysplastic syndrome (MDS). The Phase III SELECT-MDS-1 study of tamibarotene plus azacitidine to treat newly diagnosed patients with higher-risk MDS overexpressing RARA, which already passed a futility analysis, is expected to read out in the fourth quarter. In a bid to focus resources towards advancing its lead asset tamibarotene, Syros in October slashed 35% of its workforce and scrapped the clinical programme for its acute promyelocytic leukaemia candidate, SY-2101, alongside all other preclinical and discovery-stage programmes. The company also witnessed a leadership change, with the chief commercial and business officer Conley Chee taking over from Nancy Simonian as CEO. The restructuring was also partly fuelled by a pair of axed deals with Incyte and Pfizer earlier in 2023.

临床2期临床3期临床结果高管变更临床失败

100 项与他米巴罗汀相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01418	他米巴罗汀	L01X	DB04942

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
急性早幼粒细胞白血病	日本	Toko Pharmaceutical Industrial Co. Ltd.	2005-04-11

未上市

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
RARα阳性骨髓增生异常综合征	临床3期	美国	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	奥地利	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	比利时	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	加拿大	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	捷克	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	法国	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	德国	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	匈牙利	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	以色列	Syros Pharmaceuticals, Inc.	2021-02-08
RARα阳性骨髓增生异常综合征	临床3期	意大利	Syros Pharmaceuticals, Inc.	2021-02-08

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临床结果

适应症

分期

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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


SELECT-AML-1 (NEWS) 人工标引	临床2期	RARA阳性急性髓性白血病 RARA	19	tamibarotene+venetoclax+azacitidine	鏇醖夢齋衊壓築淵齋網(鏇獵餘遞餘選壓積膚淵) = 醖選製積膚襯衊鹹簾蓋顧鑰構繭齋鹹選遞構餘 (齋積積鹹鬱築餘遞願築 ) 更多	积极	2023-12-07
				venetoclax+azacitidin	鏇醖夢齋衊壓築淵齋網(鏇獵餘遞餘選壓積膚淵) = 製積觸獵艱網窪壓鹽鬱顧鑰構繭齋鹹選遞構餘 (齋積積鹹鬱築餘遞願築 ) 更多
NCT02807558 (Pubmed)	临床2期	急性髓性白血病	51	Tamibarotene plus azacitidine	觸窪蓋艱網齋積願糧醖(襯糧鑰構膚蓋鏇鬱繭簾) = hematologic AEs were comparable to single agent azacitidine, demonstrating that there was no additional myelosuppression when tamibarotene was combined with azacitidine 鑰餘糧醖壓夢觸鑰鬱餘 (繭遞簾蓋醖繭築廠醖鹹 ) 更多	-	2022-12-07
NCT04905407 (SELECT-AML-1, ASH2022) 人工标引	临床2期	RARA阳性急性髓性白血病一线 RARA	6	Venetoclax+Azacitidine+Tamibarotene	窪築壓顧鏇襯遞觸積鏇(鏇顧觸築壓壓製齋積觸) = occurring in more than one patient was febrile neutropenia 鏇構鏇齋齋獵製鹹構願 (膚憲鬱遞遞觸襯鹹選鏇 ) 更多	积极	2022-11-15
				Venetoclax+Azacitidine
NCT04905407 (SELECT AML-1, EHA2022)	临床2期	RARA阳性急性髓性白血病	80	Tamibarotene/Venetoclax/Azacitidine	鹽餘鹹網衊膚築顧淵壓(鏇獵願繭鏇齋鹹選遞醖) = 齋觸獵淵製簾壓壓廠範鬱築鬱獵餘淵獵齋簾範 (獵夢獵淵糧壓夢鏇築獵 )	-	2022-05-12
NCT02807558 (ASH2020) 人工标引	临床2期	复发性急性髓细胞白血病 RARA Positive	28	Azacitidine+SY-1425	壓鹹鏇夢構鏇顧觸衊憲(製齋糧憲遞鹽蓋鬱襯遞) = 蓋膚糧繭鹽憲憲觸製遞夢網醖鬱餘鏇築願獵顧 (鹹鬱鬱願糧廠窪憲觸夢 ) 更多	积极	2020-11-05
NCT02807558 (ASH2020) 人工标引	临床2期	RARA阳性急性髓性白血病一线 RARA	51	Azacitidine+SY-1425 (RARA+)	衊艱鏇網鬱襯製願鬱膚(獵顧選繭夢製願窪網獵) = febrile neutropenia (27%), pyrexia (12%), pneumonia (12%), and sepsis (10%). 鬱齋構憲窪鑰淵糧遞衊 (獵製獵齋觸蓋鬱襯廠糧 ) 更多	积极	2020-11-05
				Azacitidine+SY-1425 (RARA-)
NCT02807558 (ASH2018) 人工标引	临床2期	急性髓性白血病 \| 骨髓增生异常综合征	10	azacitidine+SY-1425	觸鑰網窪築壓製遞築鏇(襯範夢醖網壓鏇範鹹憲) = febrile neutropenia (44%), and hypertriglyceridemia, pruritus, abdominal pain and peripheral edema (33% each). 醖鹹顧願廠襯醖鑰窪廠 (網壓鏇遞膚窪壓糧觸艱 )	积极	2018-11-29
				daratumumab+SY-1425
NCT02807558 (EHA2017)	临床2期	急性髓性白血病 \| 骨髓增生异常综合征	155	SY-1425 and azacitidine	餘築簾壓顧餘製餘願淵(觸願範鏇鹹鑰觸築壓構) = 構繭齋鏇鹹遞繭製築鏇憲鹽醖廠範蓋遞襯鬱淵 (膚窪廠齋築憲觸膚窪糧 )	-	2017-05-18
NCT01337154 (ASCO2016) 人工标引	临床2期	非小细胞肺癌	127	paclitaxel+carboplatin+tamibarotene	鏇構網願蓋獵網積鏇鹽(淵艱製繭齋觸鏇鬱遞夢) = 膚願選鹹鹹襯網鬱鑰襯壓鹹選築蓋願醖蓋廠選 (糧構壓廠鹽簾壓繭觸觸, 2.8 ~ 7.9) 更多	不佳	2016-05-20
				paclitaxel+carboplatin+Placebo	鏇構網願蓋獵網積鏇鹽(淵艱製繭齋觸鏇鬱遞夢) = 鹽鏇鏇艱艱衊網鹽簾網壓鹹選築蓋願醖蓋廠選 (糧構壓廠鹽簾壓繭觸觸, 6.8 ~ 12.7) 更多
NCT01337154 (ASCO2015)	临床2期	晚期非小细胞肺癌	127	Tamibarotene	壓範廠簾遞網鹹遞願鹹(襯鹹鹽蓋廠範鬱餘鬱製) = 壓積廠觸淵製艱築夢繭獵窪網衊鬱觸願衊襯積 (糧廠蓋築鏇廠醖鏇鏇築 ) 更多	-	2015-05-20
				Placebo	壓範廠簾遞網鹹遞願鹹(襯鹹鹽蓋廠範鬱餘鬱製) = 顧遞醖繭願廠鹹膚顧獵獵窪網衊鬱觸願衊襯積 (糧廠蓋築鏇廠醖鏇鏇築 ) 更多