Delving into the Latest Updates on Tamibarotene with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Amnolake, Retinobenzoic acid, Tamibaro

+ [19]

Target

RARα

Mechanism

RARα agonists(Retinoic acid receptor alpha agonists)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesOther Diseases+ [2]

Active Indication

Acute Promyelocytic LeukemiaRARA positive Myelodysplastic SyndromePolycystic Kidney, Autosomal Dominant+ [1]

Inactive Indication

Advanced Hepatocellular CarcinomaAdvanced Lung Non-Small Cell CarcinomaBreast Cancer+ [7]

Originator Organization

Nippon Shinyaku Co., Ltd.

Active Organization

Syros Pharmaceuticals, Inc.

Rege Nephro Co. Ltd.StartupToko Pharmaceutical Industrial Co. Ltd.

Inactive Organization

LadRx Corp.R&R, Inc.

Zeria Pharmaceutical Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

JP (11 Apr 2005),

Acute Promyelocytic Leukemia

RegulationOrphan Drug (US), Fast Track (US), Orphan Drug (EU)

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Structure

Molecular FormulaC22H25NO3

InChIKeyMUTNCGKQJGXKEM-UHFFFAOYSA-N

CAS Registry94497-51-5

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.

22 Jul 2024·BRITISH JOURNAL OF CANCER

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

Article

Author: 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 ; Yamamoto, Masami ; Hase, Tetsunari ; 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.

28 Jun 2024·MEDICINE

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

Article

Author: 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.

85

News (Medical) associated with Tamibarotene

07 Oct 2024

·www.prnewswire.com

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

Cell TherapyPhase 2

27 Aug 2024

·www.businesswire.com

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 .

Phase 2ASH

13 Aug 2024

·firstwordpharma.com

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.

Phase 2Phase 3Clinical ResultExecutive ChangeClinical Trial Failure

100 Deals associated with Tamibarotene

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External Link

KEGG	Wiki	ATC	Drug Bank
D01418	Tamibarotene	L01X	DB04942

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute Promyelocytic Leukemia	JP	Toko Pharmaceutical Industrial Co. Ltd.	11 Apr 2005

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
RARA positive Myelodysplastic Syndrome	Phase 3	US	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	AT	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	BE	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	CA	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	CZ	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	FR	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	DE	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	HU	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	IL	Syros Pharmaceuticals, Inc.	08 Feb 2021
RARA positive Myelodysplastic Syndrome	Phase 3	IT	Syros Pharmaceuticals, Inc.	08 Feb 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SELECT-AML-1 (NEWS) Manual	Phase 2	RARA positive Acute Myeloid Leukemia RARA	19	tamibarotene+venetoclax+azacitidine	nldnigaiya(ibehschkbb) = pazaywzmhh zzbywxczgw (rrvmevvpae ) View more	Positive	07 Dec 2023
				venetoclax+azacitidin	nldnigaiya(ibehschkbb) = trsfkxvahh zzbywxczgw (rrvmevvpae ) View more
NCT02807558 (Pubmed)	Phase 2	Acute Myeloid Leukemia	51	Tamibarotene plus azacitidine	rbksvlqxpu(bsiqpdoajh) = hematologic AEs were comparable to single agent azacitidine, demonstrating that there was no additional myelosuppression when tamibarotene was combined with azacitidine xlqfcukefc (ozvzcxrfuq ) View more	-	07 Dec 2022
NCT04905407 (SELECT-AML-1, ASH2022) Manual	Phase 2	RARA positive Acute Myeloid Leukemia First line RARA	6	Venetoclax+Azacitidine+Tamibarotene	hdqtnynvxu(jspvivqrqw) = occurring in more than one patient was febrile neutropenia tumaeiygty (ibktscrivn ) View more	Positive	15 Nov 2022
				Venetoclax+Azacitidine
NCT04905407 (SELECT AML-1, EHA2022)	Phase 2	RARA positive Acute Myeloid Leukemia	80	Tamibarotene/Venetoclax/Azacitidine	muazjhklov(xenpqjbvsi) = fbusbhddla szroratifj (lzdsjojipi )	-	12 May 2022
NCT02807558 (ASH2020) Manual	Phase 2	RARA positive Acute Myeloid Leukemia First line RARA	51	Azacitidine+SY-1425 (RARA+)	gcmfseojlz(bqhrtgxzyv) = febrile neutropenia (27%), pyrexia (12%), pneumonia (12%), and sepsis (10%). zhatlrgrsq (ynqhjzvtic ) View more	Positive	05 Nov 2020
				Azacitidine+SY-1425 (RARA-)
NCT02807558 (ASH2020) Manual	Phase 2	Relapsing acute myeloid leukemia RARA Positive	28	Azacitidine+SY-1425	ltxexvwbxx(zmjxdbojln) = ydyinolijx uzlirtztft (redrhupxhl ) View more	Positive	05 Nov 2020
NCT02807558 (ASH2018) Manual	Phase 2	Acute Myeloid Leukemia \| Myelodysplastic Syndromes	10	azacitidine+SY-1425	xkpsxbksug(avmiujtedz) = febrile neutropenia (44%), and hypertriglyceridemia, pruritus, abdominal pain and peripheral edema (33% each). ykmwlvgdwn (lpfrofmdaa )	Positive	29 Nov 2018
				daratumumab+SY-1425
NCT02807558 (EHA2017)	Phase 2	Acute Myeloid Leukemia \| Myelodysplastic Syndromes	155	SY-1425 and azacitidine	hxgvhbovwr(gtgfglteyn) = qyjisihmzd mqygamlnbq (vliojpivti )	-	18 May 2017
NCT01337154 (ASCO2016) Manual	Phase 2	Non-Small Cell Lung Cancer	127	paclitaxel+carboplatin+tamibarotene	hrjeyxedwh(wclfzwvnvm) = bvhtfhzlfm zevsfwjnhl (ibabsqsxdq, 2.8 - 7.9) View more	Negative	20 May 2016
				paclitaxel+carboplatin+Placebo	hrjeyxedwh(wclfzwvnvm) = ncrkeinafg zevsfwjnhl (ibabsqsxdq, 6.8 - 12.7) View more
NCT01337154 (ASCO2015)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	127	Tamibarotene	wvhawcvbeu(xrziibmuii) = cepwiaszog zkbplrbsok (ofgqijxksf ) View more	-	20 May 2015
				Placebo	wvhawcvbeu(xrziibmuii) = gqnelbtlsh zkbplrbsok (ofgqijxksf ) View more