| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Nelutroctiv targets the cardiac troponin complex, specifically enhancing the sensitivity of troponin to calcium ions. By binding to cardiac troponin, it promotes the interaction between actin and myosin, leading to increased contractility of cardiac muscle without affecting heart rate. Some sources also mention that it may have selectivity for activin receptor-like kinase-2 (ALK2), suggesting a potential multi-faceted mechanism.
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| ln Vitro |
In vitro, Nelutroctiv acts as a direct activator of cardiac sarcomeres. It enhances the calcium sensitivity of reconstituted troponin complexes, leading to increased force generation in isolated cardiac muscle fibers. The compound's ability to promote actin-myosin interaction is measured in a cell-free system using purified contractile proteins. These in vitro assays confirm its direct mechanism of action on the fundamental contractile apparatus of the heart.
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| ln Vivo |
In vivo, Nelutroctiv has been shown to be orally active and selective for the heart. In animal models, administration of the compound leads to a concentration-dependent increase in cardiac function, as measured by echocardiography. An optimized lead compound related to Nelutroctiv showed improved pharmacokinetic profiles and a reduced potential for drug-drug interactions compared to myosin activators. It increases fractional shortening in echocardiography assessments.
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| Enzyme Assay |
For non-cell-based binding assays, standard protocols involve radioligand binding assays using recombinant human troponin C. The compound is incubated with varying concentrations of calcium and the troponin complex. Alternatively, a surface plasmon resonance (SPR) assay can be used to directly measure binding affinity and kinetics between Nelutroctiv and immobilized troponin components. A scintillation proximity assay (SPA) is also a standard method to quantify compound-receptor interactions in a homogeneous format.
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| Cell Assay |
For in vitro cell assays, isolated primary rat or human cardiomyocytes are used. Cells are plated in multi-well plates and allowed to stabilize. Nelutroctiv is then added to the culture media in a concentration range (e.g., 0.1-100 microM). Cardiomyocyte contractility is measured using a video edge detection system or a high-content imaging system. Calcium transient amplitude is also measured using calcium-sensitive fluorescent dyes like Fura-2 AM to confirm the mechanism of action.
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| Animal Protocol |
For in vivo animal models, Nelutroctiv is typically administered orally to rodents (mice or rats) via gavage. A typical dosing range is 1-30 mg/kg. Cardiac function is assessed by transthoracic echocardiography to measure parameters such as left ventricular ejection fraction (LVEF) and fractional shortening (FS). Blood samples are collected at various time points for pharmacokinetic analysis. Terminal pharmacodynamic endpoints include heart weight and histological analysis.
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| ADME/Pharmacokinetics |
A Phase 1 clinical trial has been conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of Nelutroctiv (CK-3828136) in healthy participants. The study was randomized, double-blind, and placebo-controlled, involving both single and multiple ascending doses. Nelutroctiv exhibits moderate blood-brain barrier permeability with a brain-to-plasma ratio of 3.7 at 4 hours in preclinical models. It has improved drug-like properties and oral bioavailability.
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| Toxicity/Toxicokinetics |
Nelutroctiv has undergone evaluation in Phase 1 clinical trials to assess its safety and tolerability in healthy volunteers. The results help establish a safety profile for the compound. As a drug candidate for heart failure, standard toxicology studies would include repeat-dose toxicity studies in rodents and dogs, genotoxicity assays, and safety pharmacology studies (e.g., hERG assay for cardiac safety). No specific toxicity data has been published in the public domain.
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| Additional Infomation |
Nelutroctiv is a clinical-stage drug candidate under investigation for the treatment of heart failure. It is not yet approved for clinical use. The compound is also known as CK-136, CK-3828136, and AMG-594. The mechanism of action involves activating cardiac sarcomeres by increasing troponin C's sensitivity to calcium, which is distinct from other inotropic agents that affect heart rate or intracellular calcium levels directly.
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| Molecular Formula |
C24H22F5N3O4S
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|---|---|
| Molecular Weight |
543.506202220917
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| Exact Mass |
543.125
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| CAS # |
2299177-09-4
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| PubChem CID |
137543908
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CS(=O)(=O)C1=CN=CC(=C1)C(=O)N2[C@@H]3C[C@@H]3C[C@@H]2C(=O)N[C@H](C4CC4)C5=CC(=C(C=C5F)C(F)(F)F)F
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| InChi Key |
BDIJXTIDFAIBQF-OOCUOIDPSA-N
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| InChi Code |
InChI=1S/C24H22F5N3O4S/c1-37(35,36)14-4-13(9-30-10-14)23(34)32-19-5-12(19)6-20(32)22(33)31-21(11-2-3-11)15-7-18(26)16(8-17(15)25)24(27,28)29/h4,7-12,19-21H,2-3,5-6H2,1H3,(H,31,33)/t12-,19-,20-,21-/m1/s1
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| Chemical Name |
(1R,3R,5R)-N-[(R)-cyclopropyl-[2,5-difluoro-4-(trifluoromethyl)phenyl]methyl]-2-(5-methylsulfonylpyridine-3-carbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxamide
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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) |
DMSO : ~100 mg/mL (~183.99 mM)
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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 | 1.8399 mL | 9.1995 mL | 18.3989 mL | |
| 5 mM | 0.3680 mL | 1.8399 mL | 3.6798 mL | |
| 10 mM | 0.1840 mL | 0.9199 mL | 1.8399 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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