| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
EMD57033 targets cardiac troponin C (cTnC), a calcium-binding protein that regulates muscle contraction in cardiac and slow skeletal muscle. By binding to cTnC, EMD57033 acts as a dominant Ca2+ sensitizer, increasing the sensitivity of the contractile apparatus to calcium without changing the calcium transient. The compound also binds to an allosteric pocket in the myosin motor domain, increasing basal and actin-activated myosin ATPase activity. This dual mechanism enhances myocardial contractility.
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| ln Vitro |
(+)-EMD 57033 (30 μM) decreases VIDD (ventilator-induced diaphragm fiber dysfunction) and returns Ca2+ activity and sensitivity in swine single muscle fibers [2]. In rabbit hearts, at heart rates of 100 bpm and 150 bpm, (+)-EMD 57033 (5.0-5.8 μM; 10-15 min) significantly increased coronary blood flow and myocardial V̭o2 (O2 consumption) in a concentration-dependent manner ( [Ca2+]0=1.0 or 2.5 mM). [/3]. Left ventricular (LV) end-diastolic pressure rises and diastolic duration is prolonged by (+)-EMD 57033 (5.0–5.8 μM; 10-15 minutes) [3].
In vitro, EMD57033 acts as a cardiac troponin C activator, increasing the sensitivity of the contractile apparatus to calcium. It binds to the cardiac/slow skeletal troponin C isoform and exerts myocardial contractile promotion function. EMD57033 also increases basal and actin-activated myosin ATPase activity and contractile force in striated muscles. At concentrations ≥30 μM, EMD57033 decreases the force decay during relaxation in skinned carotid artery and taenia cecum from guinea pigs. |
| ln Vivo |
(+)-EMD 57033 (0.4 or 0.8 mg/kg/min; intravenous infusion; over 20 minutes) preserves significant energy without impairing the function of dogs' diastole while improving contractility and achieving Ca2+ sensitization in intact failing hearts[4].
In vivo, EMD57033 augments the contractility in porcine myocardium by promoting the activation of myosin in thick filaments. It increases contractility at submaximal and systolic calcium concentrations. The dual effects of EMD on activating myosin heads and the troponin complex provides a proof of concept for the use of small molecule muscle activators for augmenting contractility in heart failure. However, specific in vivo efficacy data are limited in the available literature. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for EMD57033 are not typical because it targets protein-protein interactions rather than enzyme activity. However, its binding to cardiac troponin C can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure binding affinity. The compound's ability to increase myosin ATPase activity can be assessed using purified myosin and actin in the presence of ATP, measuring the rate of phosphate release.
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| Cell Assay |
In vitro cellular assays for EMD57033 are performed using cardiac myocytes or skinned muscle fibers. Cells are treated with varying concentrations of EMD57033, and contractile force is measured using force transducers. Calcium sensitivity is assessed by measuring force generation at different calcium concentrations. The compound's effects on myosin ATPase activity can be assessed in cell lysates or purified protein preparations.
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| Animal Protocol |
Animal/Disease Models: Mongrel dogs with a micromanometer implanted at the apex of the left ventricle (LV) through lateral thoracotomy [4]
Doses: 0.4 or 0.8 mg/kg/min Route of Administration: intravenous (iv) (iv)drip; infusion over 20 Minute Experimental Results: Contractility was enhanced at both doses, with similar changes occurring in CON (conscious dogs) and HF (heart failure dogs) hearts. Reduces end-diastolic pressure (EDP) and reduces arterial load or preload by 0.8 mg/kg/min. In vivo animal experiments for EMD57033 are conducted in porcine models of heart failure. Animals are administered EMD57033 via intravenous infusion, and cardiac contractility is assessed by measuring hemodynamic parameters such as left ventricular pressure and ejection fraction. The compound's effects on myocardial contractility at submaximal and systolic calcium concentrations are evaluated. However, detailed protocols are not extensively documented in the available literature. |
| ADME/Pharmacokinetics |
EMD57033 has a molecular weight of 454.52 g/mol and a molecular formula of C27H26N2O5. It is a thiadiazinone compound. The compound should be stored under recommended conditions. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been extensively reported. As a research compound, EMD57033 is primarily used in in vitro studies.
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| Toxicity/Toxicokinetics |
The toxicological profile of EMD57033 has not been extensively characterized. As a cardiac troponin C activator, the compound may have potential effects on cardiac function, including arrhythmias at high doses. No significant toxicity has been reported in the available literature. Standard toxicology studies would be necessary to establish its safety profile. The compound is a research tool and is not intended for human use.
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| References |
[1]. Wang X, et al. Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033. J Biol Chem. 2001 Jul 6;276(27):25456-66.
[2]. Ochala J, et al. EMD 57033 partially reverses ventilator-induced diaphragm muscle fibre calcium desensitisation. Pflugers Arch. 2010 Feb;459(3):475-83. [3]. Hgashiyama A, et al. Effects of EMD 57033 on contraction and relaxation in isolated rabbit hearts. Circulation. 1995 Nov 15;92(10):3094-104. [4]. Senzaki H, et al. Improved mechanoenergetics and cardiac rest and reserve function of in vivo failing heart by calcium sensitizer EMD-57033. Circulation. 2000 Mar 7;101(9):1040-8. |
| Additional Infomation |
EMD57033 is a cardiac troponin C (cTnC) activator and a dominant Ca2+ sensitizer. It is also known as (+)-EMD 57033. EMD57033 binds to the cardiac/slow skeletal troponin C isoform and exerts myocardial contractile promotion function. It also binds to an allosteric pocket in the myosin motor domain and increases myosin ATPase activity. EMD57033 is a research compound for studying cardiac contractility and is not an approved drug.
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| Molecular Formula |
C22H23N3O4S
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| Molecular Weight |
425.50072
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| Exact Mass |
425.14
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| CAS # |
147527-31-9
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| PubChem CID |
187079
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| Appearance |
White to off-white solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
687
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IZLRMTJLQCLMKF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N3O4S/c1-13-20(23-24-22(27)30-13)15-6-8-17-14(11-15)5-4-10-25(17)21(26)16-7-9-18(28-2)19(12-16)29-3/h6-9,11-13H,4-5,10H2,1-3H3,(H,24,27)
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| Chemical Name |
5-[1-(3,4-dimethoxybenzoyl)-3,4-dihydro-2H-quinolin-6-yl]-6-methyl-3,6-dihydro-1,3,4-thiadiazin-2-one
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| Synonyms |
EMD 57033; EMD-57033; EMD57033
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3502 mL | 11.7509 mL | 23.5018 mL | |
| 5 mM | 0.4700 mL | 2.3502 mL | 4.7004 mL | |
| 10 mM | 0.2350 mL | 1.1751 mL | 2.3502 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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