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 InfarctionAngina, Stable+ [2]

Inactive Indication

Acute-On-Chronic Liver Failure

Originator Organization

Les Laboratoires Servier SAS

Active Organization

Kyoto Pharmaceutical Industries Ltd.

Woolsey Pharmaceuticals, Inc.Startup

Servier Tianjin Pharmaceutical Co. Ltd.

+ [1]

Inactive Organization

Les Laboratoires Servier SAS

Drug Highest PhaseApproved

First Approval Date

JP (31 Jan 1968),

Angina PectorisMyocardial Infarction

RegulationOrphan Drug (US), Priority Review (CN)

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Structure

Molecular FormulaC14H24Cl2N2O3

InChIKeyVYFLPFGUVGMBEP-UHFFFAOYSA-N

CAS Registry13171-25-0

Trimetazidine (TMZ) is a beneficial and well-tolerable anti-anginal drug which has protective action towards ischemia and reperfusion injury. TMZ performs its anti-ischemic effect by modifying cardiac metabolism without shifting the hemodynamic functions, so it represents an outstanding complementary perspective to the general angina treatment. TMZ possesses a positive impact on the inflammatory profile, and also endothelial function furthermore displays various benefits through minimising the number, as well as the intensity of angina strikes and ameliorating the clinical indication and symptoms of myocardium ischemia. It is administrated as monotherapy along with a combination of different antianginal drugs. Apart from anti-angina action, in recent years TMZ has shown various pharmacological activities such as neuroprotective, renal protective, hepato-protective, cardio-protective effects, and other beneficial pharmacological activities. We select to write the present review article to cover the different pharmacological and therapeutic potentials of TMZ.

01 Nov 2024·Lung Cancer

Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming

Article

Author: Tse, Hung-Fat ; Lam, Stephen T S ; Yiu, Kai-Hang ; Lam, Stephen T.S. ; Chan, Yap-Hang ; Ma, Edmond S K ; Cheung, Bernard M.Y. ; Au Yeung, Shiu-Lun ; Sin, Chun-Fung ; Ma, Edmond S.K. ; Yuen-Ting, Cheng ; Cheung, Bernard M Y ; Ho, Chung-Man

BACKGROUNDMetabolic re-wiring with preferential fatty acid oxidation has been observed in lung cancer cells. Whether the use of trimetazidine, an anti-anginal agent that inhibits fatty acid oxidation, alters clinical outcomes in ischemic heart disease (IHD) patients with lung cancers is unknown.METHODSWe carried out this territory-wide, retrospective cohort study of 279,894 IHD patients prescribed with trimetazidine or long-acting oral nitrates in Hong Kong (population coverage of 7.5 millions, January 1999 - December 2020). A total of 6561 patients with pre-existing or de novo lung cancers were identified. Clinical outcomes of all-cause mortality were longitudinally compared between lung cancer patients who received trimetazidine (n = 547) versus non-users (control, n = 6014).RESULTSOver 902.9 ± 1410.6 days, lower incidence of deaths occurred in the trimetazidine group (79.0 %, n = 432/547) compared to controls (90.5 %, n = 5442/6014, P < 0.001). Kaplan-Meier analyses showed that trimetazidine use was associated with significantly higher survival from all-cause mortality in IHD patients (trimetazidine: mean survival = 1840.6 [95 %CI 1596.0-2085.3], versus control: 1056.7 [95 %CI 1011.3-1102.0] days, Log Rank = 69.4, P < 0.001). Cox regression showed that trimetazidine use was significantly associated with reduced risk of all-cause mortality in crude (HR = 0.60 [95 %CI: 0.53 to 0.68], P < 0.001) and multivariable models (HR = 0.65 [95 % CI: 0.57 to 0.74], P < 0.001). Pre-specified analyses amongst patients with pre-existing lung cancers yielded similar findings (HR = 0.49 [95 %CI: 0.35 to 0.67], P < 0.001). Survival benefits related to trimetazidine use was predominantly restricted to non-cardiovascular mortality (P < 0.001).CONCLUSIONSTrimetazidine use is associated with higher overall survival in IHD patients with lung cancers, particularly from non-cardiovascular death. These findings need to be confirmed by randomized controlled trials.

01 Nov 2024·Biochemical Pharmacology

Trimetazidine attenuates Ischemia/Reperfusion-Induced myocardial ferroptosis by modulating the Sirt3/Nrf2-GSH system and reducing Oxidative/Nitrative stress

Article

Author: Yin, Yunfei ; Tan, Mingyue ; Jiang, Tingbo ; Chen, Weixiang ; Jiang, Bin ; Jin, Yifeng ; Zhang, Jun ; Zhang, Lei ; Zhang, Yue ; Li, Hongxia

Ferroptosis is a newly defined mode of cellular demise. The increasing investigation supports that ferroptosis is a crucial factor in the complex mechanisms of myocardial ischemia-reperfusion (I/R) injury. Hence, targeting ferroptosis is a novel strategy for treating myocardial injury. Although evidence suggests that trimetazidine (TMZ) is potentially efficacious against myocardial injury, the exact mechanism of this efficacy is yet to be fully elucidated. This study aimed to determine whether TMZ can act as a ferroptosis resistor and affect I/R-mediated myocardial injury. To this end, researchers have constructed in vitro and in vivo models of I/R using H9C2 cardiomyocytes, primary cardiomyocytes, and SD rats. Here, I/R mediated the onset of ferroptosis in vitro and in vivo, as reflected by excessive iron aggregation, GSH depletion, and the increase in lipid peroxidation. TMZ largely reversed this alteration and attenuated cardiomyocyte injury. Mechanistically, we found that TMZ upregulated the expression of Sirt3. Therefore, we used si-Sirt3 and 3-TYP to interfere with Sirt3 action in vitro and in vivo, respectively. Both si-Sirt3 and 3-TYP partly mitigated the inhibitory effect of TMZ on I/R-mediated ferroptosis and upregulated the expression of Nrf2 and its downstream target, GPX4-SLC7A11. These results indicate that TMZ attenuates I/R-mediated ferroptosis by activating the Sirt3-Nrf2/GPX4/SLC7A11 signaling pathway. Our study offers insights into the mechanism underlying the cardioprotective benefits of TMZ and establishes a groundwork for expanding its potential applications.

12

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

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Angina Pectoris	Phase 1	BR	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Phase 1	UA	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Phase 1	AR	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Phase 1	VN	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Discovery	AU	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Discovery	HR	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Discovery	BY	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Discovery	RU	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Discovery	GR	Les Laboratoires Servier SAS	11 Sep 2014
Angina Pectoris	Discovery	ES	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


ESC2024	Not Applicable	Atrial Fibrillation	-	Trimetazidine	gclgklyjsf(eqjtrhxssh) = lhyjrstnnv afjseijedq (jnhemrnret ) View more	Positive	30 Aug 2024
				Long-acting nitrates	gclgklyjsf(eqjtrhxssh) = affxwkokvp afjseijedq (jnhemrnret ) View more
ESC2024	Not Applicable	-	-	Trimetazidine 80 mg/day	(djbuxprjml) = nczjibiadh ywdxdbzwfy (pozprqurvn, 38 - 46)	-	11 May 2024
ESC2024	Not Applicable	Heart Failure	2,552	Trimetazidine	(rfdaigufrx) = plpwxgimnh xrqaadylyq (fdmyepdvvg, 103 - 112m) View more	Positive	11 May 2024
ESC2023	Not Applicable	COVID-19	29	Trimetazidine	(fvxxfxxhbd) = szcnyevnxq ayaghxnort (wrnkjwpezn, 9 - 36)	-	20 May 2023
				Quadruple therapy	(fvxxfxxhbd) = iddwwiegfo ayaghxnort (wrnkjwpezn, 20 - 38)
EUCTR2018-002170-52-NL (DoPING-HFpEF, ESC2022) Manual	Phase 2	Heart Failure	25	Trimetazidine	(hyliyjbhit) = kglojyaalm zctzhfisti (glyzrffatr, 4)	Negative	27 Aug 2022
				Placebo	-
NCT02826616 (Pubmed)	Not Applicable	ST Elevation Myocardial Infarction	-	Trimetazidine	ytrucjcwvy(rhgtpggnsu) = aivjyslzgy jijgcbxqwu (vtcsbhgnhe ) View more	Positive	12 Nov 2021
				Placebo	ytrucjcwvy(rhgtpggnsu) = yzrjueobam jijgcbxqwu (vtcsbhgnhe ) View more
ESC2021	Not Applicable	Heart Failure, Diastolic	74	Trimetazidine	rvfhnitkps(slkltctjzj) = xvjxkgoddu bgwlmundxf (nkrbusgxmk ) View more	-	29 Jun 2021
				trimetazidine	rvfhnitkps(slkltctjzj) = gszxywkiry bgwlmundxf (nkrbusgxmk ) View more
EAN	Not Applicable	-	-	Trimetazidine	(qeslyaqmvs) = eszqnowngx sguvnoactw (ridoxjusdo )	-	22 May 2020
NCT03273387 (TRIMETA-PH, CTgov)	Phase 2/3	Pulmonary Arterial Hypertension	26	Placebo oral capsule (Sugar Pill)	qnhbqupfqu(zcwoppexwq) = okztmrjysn thincosnhe (zgrgtzwzab, rpbndolxsy - peazmclepd) View more	-	03 Oct 2019
				Trimetazidine (Trimetazidine)	qnhbqupfqu(zcwoppexwq) = radsmwcoaa thincosnhe (zgrgtzwzab, xxjqsgpkhy - lrefgwfnzh) View more
ESC2019	Not Applicable	estimated glomerular filtration (eGFR)	161	Trimetazidine	dgtnpzwqfm(wzohfmxcjt) = cneesoijfh vueohsxzwl (gnzxbgscvz ) View more	-	03 Sep 2019
				Trimetazidine group	dgtnpzwqfm(wzohfmxcjt) = pgsvytgiph vueohsxzwl (gnzxbgscvz ) View more