Delving into the Latest Updates on Trimetazidine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-[2,3,4-trimethoxybenzyl] piperazine dihydrochloride, Adexor, Flavedon

+ [15]

Target

ACAA2

Mechanism

ACAA2 inhibitors(acetyl-CoA acyltransferase 2 inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication

Angina PectorisMyocardial InfarctionMyocardial Ischemia+ [3]

Inactive Indication

Acute-On-Chronic Liver Failure

Originator Organization

Les Laboratoires Servier SAS

Active Organization

Woolsey Pharmaceuticals, Inc.Startup

Servier Tianjin Pharmaceutical Co. Ltd.

Martin Pharmaceuticals, Inc.Startup

+ [1]

Inactive Organization

Les Laboratoires Servier SAS

Drug Highest PhaseApproved

First Approval Date

JP (31 Jan 1968),

Angina PectorisMyocardial InfarctionMyocardial Ischemia

RegulationOrphan Drug (US), Priority Review (CN)

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Structure/Sequence

Molecular FormulaC14H24Cl2N2O3

InChIKeyVYFLPFGUVGMBEP-UHFFFAOYSA-N

CAS Registry13171-25-0

Liver fibrosis is a significant health complication with the potential to result in serious mortality and morbidity. However, there is no standard treatment due to its complex pathogenesis. The drug montelukast reversibly and selectively antagonizes the cysteinyl-leukotrienes-1 receptor and reduces inflammation; thus, it is used in the treatment of asthma. Trimetazidine, an anti-anginal agent, selectively inhibits the activity of mitochondrial long-chain 3-ketoacyl-CoA thiolase, inhibition of free fatty acid (FFA) oxidation. This study explores the efficacy of montelukast (5 and 10 mg/kg) and trimetazidine (10-20 mg/kg) against liver fibrosis induced by thioacetamide (TAA) in rats. Impaired liver function tests were significantly improved by montelukast and trimetazidine. The antioxidant and anti-inflammatory effects of montelukast and trimetazidine were proved by the inhibition of malondialdehyde (MDA) and nitric oxide (NO) accumulation, with elevation of glutathione (GSH) and superoxide dismutase activity, decreased heat shock protein (HSP-70) expression, and a decline in interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) levels in liver tissue. Also, the antifibrotic effects were explored by reducing levels of hydroxyproline and alpha-smooth muscle actin (α-SMA) expression in liver tissue and attenuating hepatic expression of hepatic expression of angiogenic mediator vascular endothelium growth factor (VEGF) and proliferative mediator Antigen Kiel 67 (Ki-67).

02 Jan 2025·Immunopharmacology and Immunotoxicology

Combined bisoprolol and trimetazidine ameliorate arsenic trioxide -induced acute myocardial injury in rats: targeting PI3K/GSK-3β/Nrf2/HO-1 and NF-κB/iNOS signaling pathways, inflammatory mediators and apoptosis

Article

Author: Abdel-Sattar, Asmaa Ramadan ; Abdel-Wahab, Basel A. ; El-Shoura, Ehab A. M. ; Ahmed, Yasmin M. ; Kozman, Magy R.

BACKGROUNDArsenic-trioxide (ATO) is an effective therapy for acute promyelocytic leukemia. Unfortunately, its utility is hindered by the risk of myocardial injury. Both bisoprolol (BIS) and trimetazidine (TMZ) have various pharmacological features, including anti-oxidant, anti-inflammatory, and anti-apoptotic properties.AIMThe cardioprotective effects of BIS and TMZ were studied, and their mechanistic role in ameliorating ATO-induced myocardial injury.MATERIALS AND METHODSForty male Wistar rats were randomly allotted into five groups as follows: normal control group (received normal saline, orally), ATO group (7.5 mg/kg, orally), BIS (8 mg/kg, orally), TMZ (60 mg/kg, orally), and finally combination group (BIS+TMZ+ATO). Following 21 days, samples of serum and cardiac tissues were obtained to perform biochemical, molecular, and histopathological investigations.RESULTSThe present study showed that ATO caused myocardial injury evidenced by changes in serum biomarkers (Aspatate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase-MB, and cardiac troponin-1), electrolyte imbalance, and lipid profiles alongside histopathologic changes. In addition, ATO administration significantly elevated malondialdehyde, nicotinamide adenine dinucleotide phosphate hydrogen oxidase, myloperoxidase, total nitrite, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, interleukin-6, 8-Hydroxy-2'-deoxyguanosine, nuclear factor NF-kappa-B p65 subunit, glycogen synthase kinase-3 beta, and caspase-3 expression contemporaneously with down-regulation of reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, heme oxygenase 1, nuclear factor erythroid 2-related factor 2, phosphatidylinositol-3 kinase, p-PI3K, and Bcl-2 expression. Interestingly, pretreatment with BIS and TMZ significantly reversed the detrimental effects of ATO-induced myocardial injury at both cellular and molecular levels. Otherwise, combining the two drugs displayed more enhancement than each drug alone.CONCLUSIONThe present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.

01 Jan 2025·Clinical and Experimental Pharmacology and Physiology

Trimetazidine restores autophagy via lncRNA H19/AMPK in diabetic heart: Implications for its therapeutic value against diabetic cardiomyopathy

Article

Author: Hu, Yadi ; Gao, Jing ; Chen, Yan ; Ye, Xiaorong ; Fan, Danjun ; Wei, Wei

AbstractObjectivePrevious studies have shown that trimetazidine (TMZ) alleviates diabetes‐induced cardiac dysfunction. However, the underlying mechanism for its protective effects on cardiac function remains incompletely understood. Diminished autophagy was found in diabetic hearts, and restoration of autophagy generates cardioprotective effect. This study aims to investigate whether and how TMZ produces protective effect through increasing autophagic activity in the diabetic heart.MethodA high‐fat diet and low‐dose streptozotocin were applied to induce type 2 diabetes mellitus (T2DM) in male C57BL/6 mice, followed by treatment with TMZ for 14 weeks before cardiac function was evaluated. To mimic the diabetic condition, the neonatal rat cardiomyocytes (NRCMs) were exposed to high glucose/palmitic acid (HP) in the presence or absence of TMZ.ResultsWe found that TMZ treatment promotes autophagic flux in cardiomyocytes, which is impaired in diabetes. We further found that the AMPK and lncRNA H19 played critical roles in mediating TMZ‐induced enhancement of autophagy in cardiomyocyte. We showed that TMZ treatment restored the level of H19 and phosphorylated AMPK (p‐AMPK T172) in diabetic heart and NRCMs exposed to HP. Of note, the effect of TMZ on autophagy and p‐AMPK was abolished by knockdown of H19.ConclusionThese findings indicated that TMZ is able to recover the cardiac autophagic activity which is impaired by T2DM, and the underlying mechanism accounted for this ability is mostly likely attributed to the restored expression of H19 and AMPK activity.

13

News (Medical) associated with Trimetazidine Hydrochloride

11 Nov 2024

·www.businesswire.com

Saghmos Therapeutics Announces Presentation at the UBS Global Healthcare Conference

GREENWICH, Conn.--( BUSINESS WIRE )--Saghmos Therapeutics (Saghmos), a privately held biopharmaceutical company poised to enter a Phase 3 study of ST-62516 (trimetazidine) to reduce the risk of cardiorenal complications after PCI, announced its participation at the UBS Global Healthcare Conference. Anna Kazanchyan, MD, Founder and Chief Executive Officer, and Stephen Grant MD, Chief Regulatory Officer and Former Deputy Director, FDA, Division of Cardiology and Nephrology, are scheduled to participate in a Fireside Chat on Tuesday, November 12 th at 10:15 am Pacific Time. A live webcast of the session will be accessible at https://cc.webcasts.com/ubsx001/111124a_js/?entity=63_JDML0IP . A replay of the webcast will be available shortly after the presentation. About Saghmos Therapeutics Saghmos is developing ST-62516 (trimetazidine), a cardiorenal metabolic modulator to reduce the risk of Acute Kidney Injury (AKI) and Major Adverse Cardiac and Kidney Events (MACKE) after contrast procedures such as percutaneous coronary intervention (PCI). Over one million PCI procedures are performed annually in the US in patients with unstable angina (heart attack). About half of these patients have comorbidities which impact the safety of PCI. This is a major unmet medical need with no FDA-approved drugs available to prevent or treat AKI and MACKE. Saghmos Therapeutics is collaborating with the Duke Clinical Research Institute to optimize and operationalize the Phase 3 study for ST-62516. Forward looking statements This press release contains forward-looking statements, pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Saghmos Therapeutics’ business, intellectual property, clinical and regulatory plans, commercial potential, and the value and benefits of ST-62516. In any forward-looking statement in which Saghmos expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. Such forward-looking statements involve known and unknown risks and uncertainties, which could cause Saghmos’ actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources, uncertainties and changes related to the law and regulatory process, and general changes in the economic environment. These forward-looking statements are based on our current expectations. Saghmos does not undertake any obligation to update these forward-looking statements, except as required by applicable laws.

Phase 3

17 Sep 2024

·www.businesswire.com

Saghmos Therapeutics Announces Presentation at UBS 2024 Biotechnology Private Company Virtual Symposium

GREENWICH, Conn.--( BUSINESS WIRE )--Saghmos Therapeutics, Inc. (Saghmos), a privately held biopharmaceutical company poised to enter a Phase 3 study of ST-62516 (trimetazidine) to reduce the risk of cardiorenal complications after PCI, announced its participation at the UBS 2024 Biotechnology Private Company Virtual Symposium. Anna Kazanchyan, MD, Founder and Chief Executive Officer, and Stephen Grant MD, Chief Regulatory Officer and Former Deputy Director, FDA, Division of Cardiology and Nephrology, are scheduled to present on Wednesday, September 18 th at 10:30 AM Eastern Time. A live webcast of the session will be accessible at https://kvgo.com/ubs/saghmos-therapeutics-sept-2024 . A replay of the webcast will be available shortly after the presentation. About Saghmos Therapeutics Saghmos is developing ST-62516 (trimetazidine), a cardiorenal metabolic modulator to reduce the risk of Acute Kidney Injury (AKI) and Major Adverse Cardiac and Kidney Events (MACKE) after contrast procedures such as PCI. Over one million PCI procedures are performed annually in the US in patients with unstable angina (heart attack). About half of these patients have comorbidities which impact the safety of PCI. This is a major unmet medical need with no FDA-approved drugs available to prevent or treat AKI and MACKE. Forward looking statements This press release contains forward-looking statements, pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Saghmos Therapeutics’ business, intellectual property, clinical and regulatory plans, commercial potential, and the value and benefits of ST-62516. In any forward-looking statement in which Saghmos expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. Such forward-looking statements involve known and unknown risks and uncertainties, which could cause Saghmos’ actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources, uncertainties and changes related to the law and regulatory process, and general changes in the economic environment. These forward-looking statements are based on our current expectations. Saghmos does not undertake any obligation to update these forward-looking statements, except as required by applicable laws.

Phase 3

03 Sep 2024

·www.businesswire.com

Saghmos Therapeutics Announces Presentation at the Morgan Stanley 22nd Annual Global Healthcare Conference

GREENWICH, Conn.--( BUSINESS WIRE )--Saghmos Therapeutics, Inc. (Saghmos), a privately held biopharmaceutical company poised to enter a Phase 3 study of ST-62516 (trimetazidine) to reduce the risk of cardiorenal complications after PCI, announced its participation at the Morgan Stanley 22 nd Annual Global Healthcare Conference, to be held at the New York Marriott Marquis. Anna Kazanchyan, MD, Founder and Chief Executive Officer, and Stephen Grant MD, Chief Regulatory Officer and Former Deputy Director, FDA, Division of Cardiology and Nephrology, are scheduled to present on Wednesday, September 4 th at 2:35 pm Eastern Time. A live webcast of the session will be accessible at https://cc.webcasts.com/morg007/090424a_js/?entity=171_V63PWGF . A replay of the webcast will be available shortly after the presentation. About Saghmos Therapeutics Saghmos is developing ST-62516 (trimetazidine), a cardiorenal metabolic modulator to reduce the risk of Acute Kidney Injury (AKI) and Major Adverse Cardiac and Kidney Events (MACKE) after contrast procedures such as PCI. Over one million PCI procedures are performed annually in the US in patients with unstable angina (heart attack). About half of these patients have comorbidities which impact the safety of PCI. This is a major unmet medical need with no FDA-approved drugs available to prevent or treat AKI and MACKE. Forward looking statements This press release contains forward-looking statements, pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Saghmos Therapeutics’ business, intellectual property, clinical and regulatory plans, commercial potential, and the value and benefits of ST-62516. In any forward-looking statement in which Saghmos expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. Such forward-looking statements involve known and unknown risks and uncertainties, which could cause Saghmos’ actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources, uncertainties and changes related to the law and regulatory process, and general changes in the economic environment. These forward-looking statements are based on our current expectations. Saghmos does not undertake any obligation to update these forward-looking statements, except as required by applicable laws.

Phase 3

100 Deals associated with Trimetazidine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D01606	Trimetazidine Hydrochloride	C01EB15	DB09069

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Angina Pectoris	JP	Kyoto Pharmaceutical Industries Ltd.	31 Jan 1968
Myocardial Infarction	JP	Kyoto Pharmaceutical Industries Ltd.	31 Jan 1968
Myocardial Ischemia	JP	Kyoto Pharmaceutical Industries Ltd.	31 Jan 1968

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Angina Pectoris	Preclinical	HR	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	RS	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	PE	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	AR	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	CZ	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	PL	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	RU	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	IT	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	AU	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Preclinical	SK	Les Laboratoires Servier SAS	11 Sep 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03809273 (Pubmed) Manual	Phase 4	Coronary Disease	681	Yangxinshi	wpjunvartd(lgurzzrmwy) = yxgrizdezp zbsmmjplvy (yxtvuynkvn, 1.25) View more	Non-inferior	07 Nov 2024
				Trimetazidine	wpjunvartd(lgurzzrmwy) = xshmiauzjf zbsmmjplvy (yxtvuynkvn, 1.00) View more
ESC2024	Not Applicable	Atrial Fibrillation	-	Trimetazidine	zcjharufuz(dgwgoajbei) = hjmmvdevce xkewnjpsmy (aqyolpdwjl ) View more	Positive	30 Aug 2024
				Long-acting nitrates	zcjharufuz(dgwgoajbei) = mskpwvpacl xkewnjpsmy (aqyolpdwjl ) View more
ESC2024	Not Applicable	-	-	Trimetazidine 80 mg/day	(jbqpywujbl) = pswzbiogml ngwrlsdthj (ufcnieefsh, 38 - 46)	-	11 May 2024
ESC2024	Not Applicable	Heart Failure	2,552	Trimetazidine	(hdurxenejc) = qphegpbllc ntokjkapjg (wknqmlrbpk, 103 - 112m) View more	Positive	11 May 2024
ESC2023	Not Applicable	COVID-19	29	Trimetazidine	(twmpaairpy) = ybjmahlaty zhxmaoacgd (xmsrfaehik, 9 - 36)	-	20 May 2023
				Quadruple therapy	(twmpaairpy) = pskebkwris zhxmaoacgd (xmsrfaehik, 20 - 38)
EUCTR2018-002170-52-NL (DoPING-HFpEF, ESC 12022 \| ESC 22022) Manual	Phase 2	Heart Failure	25	Trimetazidine	(dokjqmhyre) = ucorzesfzw mtyspngjcw (gftmvizzed, 4)	Negative	27 Aug 2022
				Placebo	-
NCT02826616 (Pubmed \| Cardiovasc Drugs Ther)	Not Applicable	ST Elevation Myocardial Infarction	-	Trimetazidine	fjgiapbllb(xtuxktvhlk) = wthdcphnms nwktqjtkpg (mpdtuxulpz ) View more	Positive	12 Nov 2021
				Placebo	fjgiapbllb(xtuxktvhlk) = czjetdlwuj nwktqjtkpg (mpdtuxulpz ) View more
ESC2021	Not Applicable	Heart Failure, Diastolic	74	Trimetazidine	cahjwzwalf(qunzusajza) = vpqkgvaydn tlclyotcdj (txpcaevhre ) View more	-	29 Jun 2021
				trimetazidine	cahjwzwalf(qunzusajza) = grqunfdhed tlclyotcdj (txpcaevhre ) View more
CHOICE II (ESH2021)	Not Applicable	Angina Pectoris	221	Trimetazidine 35 mg bid	skbppqfxqj(efnmmjojlh) = owfzbkkwnr ecfeirtwin (qvsxwwddnc ) View more	Positive	01 Apr 2021
				Bisoprolol	skbppqfxqj(efnmmjojlh) = wpfokljjao ecfeirtwin (qvsxwwddnc ) View more
EAN2020	Not Applicable	-	-	Trimetazidine	(hbvmtohhri) = fiyvxmfqsz vvooyystln (ohtsdfhhgl )	-	22 May 2020