| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
| Targets |
HTS-07545 targets sulfide:quinone oxidoreductase (SQOR), a mitochondrial enzyme that catalyzes the first step in the hydrogen sulfide (H2S) oxidation pathway. By inhibiting SQOR with an IC50 of 30 nM, HTS-07545 slows down the rate at which H2S is broken down. This inhibition leads to increased H2S levels, which can have therapeutic effects in conditions such as heart failure and pancreatic ductal adenocarcinoma.
|
|---|---|
| ln Vitro |
HTS-07545 is a potent SQOR inhibitor with an IC50 of 30 nM. It selectively binds to the coenzyme Q-binding pocket of SQOR and exhibits low cytotoxicity. The compound reduces the decomposition rate of hydrogen sulfide (H2S). In cellular models, HTS-07545 has been shown to mitigate cardiac remodeling, fibrosis, and heart failure progression. It is also being studied for its potential in pancreatic ductal adenocarcinoma research.
|
| ln Vivo |
In vivo, HTS-07545 mitigates cardiac remodeling, fibrosis, and heart failure progression in animal models, offering a potential therapeutic approach for heart failure with reduced ejection fraction (HFrEF). The compound is also being investigated for its role in pancreatic ductal adenocarcinoma. By inhibiting SQOR and increasing H2S levels, the compound may exert cardioprotective and anti-fibrotic effects. Specific dosing regimens and efficacy data are determined from preclinical studies.
|
| Enzyme Assay |
The in vitro enzyme assay for HTS-07545 typically involves measuring the inhibition of SQOR enzymatic activity. Recombinant SQOR enzyme is incubated with varying concentrations of HTS-07545 (typically 0.001-100 µM) in the presence of coenzyme Q and sulfide substrate. The enzymatic activity is measured by monitoring the oxidation of sulfide or the reduction of coenzyme Q spectrophotometrically. The IC50 value (30 nM) is determined by plotting the percentage of inhibition against compound concentration.
|
| Cell Assay |
In vitro cellular assays for HTS-07545 typically involve treating cells with the compound at concentrations ranging from 0.001 to 10 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays to confirm low cytotoxicity. Cellular H2S levels are measured using fluorescent probes. The compound's effects on cellular metabolism, oxidative stress, and signaling pathways are assessed using standard biochemical assays. The compound is dissolved in DMSO and diluted in cell culture medium.
|
| Animal Protocol |
In vivo animal studies for HTS-07545 typically involve administration to mice or rats via intraperitoneal or oral routes at doses determined from preclinical studies. Heart failure models (such as pressure overload or ischemia-reperfusion) are used to evaluate efficacy. Cardiac function is assessed by echocardiography. Fibrosis is evaluated by histological staining. The compound's pharmacokinetics and pharmacodynamics are evaluated in these models.
|
| ADME/Pharmacokinetics |
HTS-07545 has a molecular weight of 358.39 g/mol and formula C22H18N2O3. It is soluble in DMSO (~100 mg/mL). Recommended storage is powder at -20°C for 3 years and in solvent at -80°C for 6 months or -20°C for 1 month. The compound has a LogP of 4.5. It appears as a powder form. Detailed PK parameters would require experimental determination.
|
| Toxicity/Toxicokinetics |
HTS-07545 exhibits low cytotoxicity and is intended for research use only, not for human therapeutic applications. Standard preclinical toxicity assessments would include acute toxicity studies in rodents, repeated-dose toxicity studies, and assessment of off-target effects. As an SQOR inhibitor that modulates H2S levels, the compound may affect normal H2S signaling pathways, which could contribute to potential toxicity. Appropriate safety precautions should be taken when handling.
|
| Additional Infomation |
HTS-07545 (CAS 118666-03-8) is a potent, first-in-class inhibitor of sulfide:quinone oxidoreductase (SQOR) with an IC50 of 30 nM. It has a molecular weight of 358.39 g/mol and formula C22H18N2O3. The compound selectively binds to the coenzyme Q-binding pocket of SQOR, exhibits low cytotoxicity, and mitigates cardiac remodeling, fibrosis, and heart failure progression in animal models. It is used in heart failure and pancreatic ductal adenocarcinoma research. HTS-07545 is also known as HTS07545 and is not approved for clinical use.
|
| Molecular Formula |
C22H18N2O3
|
|---|---|
| Molecular Weight |
358.389925479889
|
| Exact Mass |
358.131
|
| CAS # |
118666-03-8
|
| PubChem CID |
2813721
|
| Appearance |
Powder form
|
| LogP |
4.5
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
27
|
| Complexity |
517
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCOC(=O)COC1=C(C(=CC(=N1)C2=CC=CC=C2)C3=CC=CC=C3)C#N
|
| InChi Key |
PZNJITRXQKRPFY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H18N2O3/c1-2-26-21(25)15-27-22-19(14-23)18(16-9-5-3-6-10-16)13-20(24-22)17-11-7-4-8-12-17/h3-13H,2,15H2,1H3
|
| Chemical Name |
ethyl 2-(3-cyano-4,6-diphenylpyridin-2-yl)oxyacetate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~279.03 mM)
|
|---|---|
| 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 | 2.7903 mL | 13.9513 mL | 27.9026 mL | |
| 5 mM | 0.5581 mL | 2.7903 mL | 5.5805 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7903 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
