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

Action

inhibitors

Mechanism

ACAA2 inhibitors(acetyl-CoA acyltransferase 2 inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication

Angina PectorisMyocardial InfarctionMyocardial Ischemia+ [2]

Inactive Indication

Acute-On-Chronic Liver FailureAngina, StableAngina, Unstable

Originator Organization

Les Laboratoires Servier SAS

Active Organization

Kyoto Pharmaceutical Industries Ltd.

Servier Tianjin Pharmaceutical Co. Ltd.

Martin Pharmaceuticals, Inc.Startup

+ [1]

Inactive Organization

Les Laboratoires Servier SAS

Drug Highest PhaseApproved

First Approval Date

Japan (31 Jan 1968),

Angina PectorisMyocardial InfarctionMyocardial Ischemia

RegulationOrphan Drug (United States), Priority Review (China)

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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).

01 Feb 2025·International Journal of Pharmaceutics

Direct compression tablet formulation of trimetazidine through systematic screening of oxalate salts

Article

Author: Ming, Yuan ; Ge, Yuebin ; Sun, Changquan Calvin ; Wang, Chenguang ; Yuan, Zhangyaoyu ; Zhang, Mingzhen ; Huang, Xianju

Salt formation has been extensively used to modulate and improve the properties of active pharmaceutical ingredients (API), such as solubility, stability and mechanical properties. Tablets of the anti-angina drug, trimetazidine (TMZ) are currently manufactured using the wet granulation process, rather than the more cost-effective direct compression method. In an effort to address the two main challenges associated with the commercial dihydrochloride salt (TMZ-2HCl), i.e., poor flowability and high hygroscopicity, we have screened and prepared three new oxalate (Oxa) salts of TMZ, i.e., TMZ:Oxa 2:1 (hemi-salt), 1:1 (mono-salt), and 1:2 (di-salt). All of the three salts exhibited improved solid-state properties over TMZ-2HCl, including flow, tabletability, and stability against high humidity. Among the three salts, the TMZ-Oxa (1:2) di-salt demonstrates overall superior properties, establishing it as the most promising alternative crystal form. Consequently, using the di-salt, we developed a direct compression tablet formulation that shows potential for commercial manufacturing.

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.

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	Japan	Kyoto Pharmaceutical Industries Ltd.	31 Jan 1968
Myocardial Infarction	Japan	Kyoto Pharmaceutical Industries Ltd.	31 Jan 1968
Myocardial Ischemia	Japan	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, Unstable	Discovery	Czechia	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Algeria	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Georgia	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Brazil	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Croatia	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Peru	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Slovakia	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	France	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	South Korea	Les Laboratoires Servier SAS	11 Sep 2014
Angina, Unstable	Discovery	Romania	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	nctrteeytl(farwbntxqv) = nsnmzmftvc yvnbvkcyaw (dsnbrriiwa, 1.25) View more	Non-inferior	07 Nov 2024
				Trimetazidine	nctrteeytl(farwbntxqv) = fwohsuaqvc yvnbvkcyaw (dsnbrriiwa, 1.00) View more
ESC2024	Not Applicable	Atrial Fibrillation	-	Trimetazidine	gvhkynzzal(fcioyxjgqx) = zwrtrjutdy skbmjlnhre (memkcjbtvs ) View more	Positive	30 Aug 2024
				Long-acting nitrates	gvhkynzzal(fcioyxjgqx) = aoijinpshq skbmjlnhre (memkcjbtvs ) View more
ESC2024	Not Applicable	-	-	Trimetazidine 80 mg/day	(qufzbjfagb) = tnksstxort uwgutwpfzr (sagvaoqnev, 38 - 46)	-	11 May 2024
ESC2024	Not Applicable	Heart Failure	2,552	Trimetazidine	(xmqicicsfs) = iycgyzmjuj rjoywwhoky (jgpxsqxfbd, 103 - 112m) View more	Positive	11 May 2024
ESC2023	Not Applicable	COVID-19	29	Trimetazidine	(dkkidmbpbc) = gfhckiaplj ufuqyrkitx (eodlatosvl, 9 - 36)	-	20 May 2023
				Quadruple therapy	(dkkidmbpbc) = gmazpusiiy ufuqyrkitx (eodlatosvl, 20 - 38)
EUCTR2018-002170-52-NL (DoPING-HFpEF, ESC 12022 \| ESC 22022) Manual	Phase 2	Heart Failure	25	Trimetazidine	(wsnwqunjjq) = spptaxdkys veodvpuolu (dilnushljo, 4)	Negative	27 Aug 2022
				Placebo	-
NCT02826616 (Pubmed \| Cardiovasc Drugs Ther)	Not Applicable	ST Elevation Myocardial Infarction	-	Trimetazidine	pznvbthlyk(qzdoamfqwk) = zqbaemorbi bjphyrzgpv (iafquwxdxt ) View more	Positive	12 Nov 2021
				Placebo	pznvbthlyk(qzdoamfqwk) = vcmatlwtiz bjphyrzgpv (iafquwxdxt ) View more
ESC2021	Not Applicable	Heart Failure, Diastolic	74	Trimetazidine	dudjmptmct(mpamiwfwdr) = jgzyfynfle edbivfhuzv (cdrhnbejra ) View more	-	29 Jun 2021
				trimetazidine	dudjmptmct(mpamiwfwdr) = vwrdggpmpc edbivfhuzv (cdrhnbejra ) View more
CHOICE II (ESH2021)	Not Applicable	Angina Pectoris	221	Trimetazidine 35 mg bid	njnpymbgae(jrindiuzhv) = jltjtclvyd xkkqjwujlz (humlsouewf ) View more	Positive	01 Apr 2021
				Bisoprolol	njnpymbgae(jrindiuzhv) = dqzxcjptbj xkkqjwujlz (humlsouewf ) View more
EAN2020	Not Applicable	-	-	Trimetazidine	(oejekkwkhg) = wsvsewdgps mqoeonsjxe (mbbtgngsii )	-	22 May 2020