The investigators need to test the effect of Trimetazidine on the pro-inflammatory marker Interleukin - 18 , NIHSS score, and mRs score of acute ischemic stroke patients.

Start Date01 Sep 2024

Sponsor / Collaborator

Ain Shams University

TCTR20240529007 / Not yet recruitingPhase 1IIT

A Multiple-dose, Randomized, Open-label, Crossover Bioequivalence Study of Generic Trimetazidine Dihydrochloride 80 mg Prolonged-release Capsules and Reference Product in Healthy Thai Volunteers under Fed Conditions

Start Date20 Aug 2024

Sponsor / Collaborator

Bio-innova Co., Ltd

CTRI/2024/07/069720 / Not yet recruitingPhase 4

A Prospective, Multicenter, Open-label, Post-Marketing Observational Study to Evaluate the Anti-Anginal Effectiveness of Trimetazidine 60 mg Once Daily Formulation in Stable Angina Patients in Real-World Practice - NA

Start Date07 Jul 2024

Sponsor / Collaborator-

100 Clinical Results associated with Trimetazidine Hydrochloride

100 Translational Medicine associated with Trimetazidine Hydrochloride

100 Patents (Medical) associated with Trimetazidine Hydrochloride

1,300

Literatures (Medical) associated with Trimetazidine Hydrochloride

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

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.

06 Oct 2024·Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]

[Mechanism of protective effect of metformin against septic cardiomyopathy based on the P38 MAPK/JNK signaling pathway].

Article

Author: Liao, Y ; Li, L ; Liu, Z Y

Exploring the protective mechanism of metformin against septic cardiomyopathy based on the mitogen-activated protein kinase P38 (P38 MAPK)/c-Jun amino-terminal kinase (JNK) signaling pathway. This paper is an experimental animal study design, which was completed from January to December 2023 at the Xiangya Hospital, Central South University. Forty-eight 8-week-old female C57BL/6 mice were divided into four groups: group A (control group), group B (model group), group C (model+trimetazidine hydrochloride), and group D (model+metformin group), with 12 mice in each group, by using a randomized numeric table method. Groups B, C, and D were injected intraperitoneally with LPS (15 mg/kg) to construct a septic cardiomyopathy mouse model. 24 h after modeling, Groups A and B were injected intraperitoneally with an equal amount of saline, Group C was given 20 mg/kg trimetazidine hydrochloride by gavage, and Group D was injected with metformin 200 mg/kg intraperitoneally, and all of them were subjected to consecutive interventions for 14 d. The results were summarized in the following table. Ultrasound imaging system was used to detect cardiac function, and TUNEL method was used to detect apoptosis rate of myocardial tissues; real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of mRNA of JNK, P38 MAPK of P38 MAPK signaling pathway in the myocardial tissues of mice; Plasma creatine kinase isoenzyme (CK-MB), brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels were measured by enzyme-linked immunosorbent assay (ELISA) in all groups of mice; and protein kinase C, and protein kinase C levels were measured by protein blotting in cardiac muscle tissue. Eplison isoform (PKCε), and Cavity protein-3 (Cav-3) protein expression in myocardial tissues. The results showed that compared with group A, left ventricular ejection fraction (LVEF) (79.51±6.62)%, left ventricular short-axis shortening (FS) (45.66±4.13), apoptosis rate (4.34±0.36)%, JNK (0.96±0.06), P38 MAPK (1.01±0.03), CK-MB (2.37±0.13) μg/L, BNP (21.36±3.47) ng/L, TNF-α (176.22±19.24) ng/L, IL-6 (35.43±3.84) ng/L, PKCε expression (1.98±0.26), Cav-3 expression (1.04±0.03) compared to apoptosis rates in groups B, C, and D (28.22±4.49, 22.45±3.69, 15.88±3.27), JNK (1.68±0.11, 1.32±0.18, 1.13±0.14), P38 MAPK (2.47±0.71,1.77±0.35,1.49±0.05), CK-MB (16.55±2.16, 12.63±1.98, 5.27±0.61), BNP (48.92±5.67, 33.78±4.11, 27.55±3.84), TNF-α (463.71±24.81, 335.71±36.71, 214.78±22.53), and IL-6 (78.57±6.36, 63.71±5.66, 52.47±5.47) expression were elevated, while left ventricular ejection fraction (LVEF) (49.38±5.27, 55.47±5.03, 62.26±5.14), left ventricular short-axis shortening (FS) (24.36±2.17, 30.43±3.29, 33.57±2.72), PKCε expression (1.33±0.21, 1.54±0.23, 1.75±0.22), and Cav-3 expression (0.47±0.06, 0.76±0.05, 0.85±0.04) were all down-regulated (F=113.020,67.657,219.539,206.222,227.977,88.455,6285.186,135.877,65.924,96.362,17.532,314.419,P<0.05). Compared with group B, apoptosis rate, JNK, P38 MAPK, CK-MB, BNP, TNF-α, and IL-6 expression were decreased, and LVEF, FS, PKCε, and Cav-3 expression were up-regulated in groups C and D. And group D was better than group C (P<0.05). In conclusion, metformin has a protective effect against septic cardiomyopathy, and the mechanism may be related to the inhibition of the activation of the P38 MAPK/JNK signaling pathway and the up-regulation of PKCε and Cav-3 expression.

01 Oct 2024·EUROPEAN JOURNAL OF PHARMACOLOGY

New insights on pharmacological and therapeutic potentials of trimetazidine beyond anti-anginal drug: A comprehensive review

Review

Author: Akindele, Abidemi James ; Singh, Dhirendra ; Oladimeji-Salami, Joy

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.

News (Medical) associated with Trimetazidine Hydrochloride

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

05 Jun 2024

·www.biospace.com

Saghmos Therapeutics Announces Issuance of U.S. Patent for Phase 3-Ready Cardiorenal Metabolic Modulator ST-62516

ST-62516 Intended for Patients with Cardiovascular-Kidney-Metabolic (CKM) Syndrome Undergoing Procedures with Contrast Dyes Provides exclusivity through 2037 GREENWICH, Conn.--(BUSINESS WIRE)-- Saghmos Therapeutics, Inc. (Saghmos), a privately held biopharmaceutical company, announced that the U.S. Patent and Trademark Office (USPTO) has granted U.S. Patent No. 11,986,473 titled, “Prevention and/or Treatment of Contrast-Induced Acute Kidney Injury” for its Phase 3-ready product, ST-62516 (trimetazidine), a cardiorenal metabolic modulator. The patent provides exclusivity through 2037, with broad claims for the reduction of Acute Kidney Injury (AKI) and Major Adverse Cardiac and Kidney Events (MACKE) in patients undergoing procedures with contrast dyes. Saghmos is developing ST-62516 to reduce the risk of AKI and MACKE after contrast procedures such as percutaneous coronary intervention (PCI). The interrelationship between cardiovascular disease, kidney disease, and metabolic disease has recently been termed CKM Syndrome. Patients with this syndrome are at increased risk of adverse cardiovascular and kidney outcomes after contrast procedures such as PCI. ST-62516 is uniquely positioned to address this unmet need. "We are excited about the continued growth of Saghmos’ intellectual property estate, which now has two issued U.S. patents as well as an issued patent in Japan,” commented Anna Kazanchyan, MD, Founder and CEO of Saghmos Therapeutics. According to the American Heart Association, one in three US adults have three or more risk factors for CKM. Over one million PCI procedures are performed annually in the US and about half of these individuals have CKM Syndrome, or are aged 75 and older. CKM Syndrome in combination with certain procedure-related factors, adversely affects the safety of PCI and increase the risk of AKI and MACKE. This is a major unmet medical need with no FDA-approved drugs available. ST-62516 could benefit all people undergoing a PCI, not just those with CKM Syndrome, by reducing the threat of AKI and MACKE after PCI. About Saghmos Therapeutics Saghmos Therapeutics is developing ST-62516 (trimetazidine) 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). ST-62516 is poised to enter a Phase 3 study. The company recently announced a collaboration with the Duke Clinical Research Institute (DCRI) to optimize all aspects of and plan the operationalization of the Phase 3 study. 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 3AHA

100 Deals associated with Trimetazidine Hydrochloride

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.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Angina, Stable	Phase 1	CN	Servier Tianjin Pharmaceutical Co. Ltd.	21 Jan 2021
Acute-On-Chronic Liver Failure	Phase 1	AT	Martin Pharmaceuticals, Inc.Startup	28 Nov 2018
Acute-On-Chronic Liver Failure	Phase 1	BE	Martin Pharmaceuticals, Inc.Startup	28 Nov 2018
Acute-On-Chronic Liver Failure	Phase 1	FR	Martin Pharmaceuticals, Inc.Startup	28 Nov 2018
Acute-On-Chronic Liver Failure	Phase 1	DE	Martin Pharmaceuticals, Inc.Startup	28 Nov 2018
Acute-On-Chronic Liver Failure	Phase 1	ES	Martin Pharmaceuticals, Inc.Startup	28 Nov 2018
Amyotrophic Lateral Sclerosis	Preclinical	US	Woolsey Pharmaceuticals, Inc.Startup	15 Jul 2024
Pulmonary Arterial Hypertension	Preclinical	-	Martin Pharmaceuticals, Inc.Startup	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2023	Not Applicable	Angina, Unstable	-	Trimetazidine 80mg OD	jerdyxpclb(ludbzevmgy) = sxheyuogvd rfwaxtezxh (rupwbwnnzu )	Positive	27 Aug 2023
ESC2023	Not Applicable	COVID-19	29	Trimetazidine	fcbydljuis(dutvslkaor) = ubzwsldale hlyfrxryzd (qfyvalraqu, 9 - 36)	-	20 May 2023
				Quadruple therapy	fcbydljuis(dutvslkaor) = qxngmhdixa hlyfrxryzd (qfyvalraqu, 20 - 38)
EUCTR2018-002170-52-NL (DoPING-HFpEF, ESC2022) Manual	Phase 2	Heart Failure	25	Trimetazidine	melhstjzax(hhoqeooafn) = efunruhjft vmshegpyip (ykdrhlwtut, 4)	Negative	27 Aug 2022
				Placebo	-
NCT02826616 (Pubmed)	Not Applicable	ST Elevation Myocardial Infarction	-	Trimetazidine	rmnahtbmha(gmfgfapihc) = emueuwwcll aviujrvmet (jadgmlnkxp ) View more	Positive	12 Nov 2021
				Placebo	rmnahtbmha(gmfgfapihc) = qxfhvmmirg aviujrvmet (jadgmlnkxp ) View more
ESC2021	Not Applicable	Heart Failure, Diastolic	74	Trimetazidine	kvqspfguhr(rvtnqujwlz) = umjzgmujug yjpzzswcqq (bfimdozpxv ) View more	-	29 Jun 2021
				trimetazidine	kvqspfguhr(rvtnqujwlz) = cqnejkqjfe yjpzzswcqq (bfimdozpxv ) View more
NCT03273387 (TRIMETA-PH, CTgov)	Phase 2/3	Pulmonary Arterial Hypertension	26	Placebo oral capsule (Sugar Pill)	ekjupsfsus(tgoztvizpw) = oofgtcymda owavbmemkr (tsaudcorfl, xtkunigzvi - oywejhkrio) View more	-	03 Oct 2019
				Trimetazidine (Trimetazidine)	ekjupsfsus(tgoztvizpw) = rgktwhfsvv owavbmemkr (tsaudcorfl, hstwlieolv - kliwmxncfg) View more
ESC2019	Not Applicable	estimated glomerular filtration (eGFR)	161	Trimetazidine	hhyxxitcrl(empdtvvsae) = uklaudmfhe klgmdvxlqk (djmddeecnl ) View more	-	03 Sep 2019
				Trimetazidine group	hhyxxitcrl(empdtvvsae) = jmtwmkuaum klgmdvxlqk (djmddeecnl ) View more
ESC2018	Not Applicable	ST Elevation Myocardial Infarction	-	Trimetazidine	urskmztdya(uafuidfwvk) = gvphbcsfzn mxxarfuypf (eknarsgbxc ) View more	Positive	28 Aug 2018
				Standard therapy	urskmztdya(uafuidfwvk) = yiclvhgcys mxxarfuypf (eknarsgbxc ) View more
ODA trial (ESC2018)	Not Applicable	Angina, Stable	3,066	Trimetazidine 80 mg od	eeyxiusacm(qnubptcmac) = stdxrtsyrg shiyxupdrz (aojssxcntj ) View more	-	28 Aug 2018
ESC2018	Not Applicable	Reduced ejection fraction co-occurrent and due to chronic heart failure	-	Trimetazidine	gouqvuodwa(hmohdvesna) = icfsckpmac vjqobqqapn (ejsvkdzkkn ) View more	-	27 May 2018
				Standard pharmacotherapy	gouqvuodwa(hmohdvesna) = xegqmjnlic vjqobqqapn (ejsvkdzkkn ) View more

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