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| Targets |
The primary target of SMYD3-IN-1 is SMYD3 (SET and MYND domain containing 3), a histone methyltransferase that catalyzes the methylation of lysine 4 on histone H3 (H3K4) and also methylates non-histone substrates. SMYD3 plays a critical role in gene regulation by modulating chromatin structure and transcription. It is overexpressed in various cancers and has been implicated in tumor progression. SMYD3-IN-1 acts as an irreversible and selective inhibitor of SMYD3 with an IC₅0 of 11.7 nM. By irreversibly inhibiting SMYD3, the compound provides sustained suppression of its enzymatic activity, making it a valuable tool for studying SMYD3 biology.
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| ln Vitro |
In vitro studies demonstrate that SMYD3-IN-1 is an irreversible and selective inhibitor of SMYD3 with an IC₅0 of 11.7 nM. The compound potently inhibits SMYD3-mediated histone H3K4 methylation and methylation of non-histone substrates. Its irreversible mechanism of action provides sustained inhibition of SMYD3 activity. SMYD3-IN-1 is used as a research tool to study the role of SMYD3 in gene regulation, cancer, and other diseases. The compound's selectivity for SMYD3 over other methyltransferases is a key feature of its activity profile.
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| ln Vivo |
In vivo studies of SMYD3-IN-1 are limited, as it is primarily used as a research tool in cellular and biochemical assays. However, given its potent and selective inhibition of SMYD3 with an IC₅0 of 11.7 nM, the compound may have potential for in vivo efficacy studies in animal models of SMYD3-dependent diseases, such as cancer. SMYD3 is overexpressed in various cancers and has been implicated in tumor progression. Further studies are needed to evaluate its pharmacokinetic properties, bioavailability, and efficacy in vivo.
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| Enzyme Assay |
For in vitro enzyme/receptor binding assays, SMYD3-IN-1 is evaluated using methyltransferase activity assays that measure SMYD3-mediated methylation of histone H3 or other substrates. The compound is incubated with recombinant SMYD3 enzyme, S-adenosylmethionine (SAM), and substrate at various concentrations. SMYD3 activity is quantified by measuring the incorporation of methyl groups into the substrate using radiometric, fluorescence-based, or ELISA methods. IC₅0 values are determined from dose-response curves. The irreversible nature of inhibition can be confirmed by dialysis or dilution experiments. Selectivity profiling against other methyltransferases may be performed.
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| Cell Assay |
For in vitro cellular experiments, SMYD3-IN-1 is tested in cell lines expressing SMYD3 to evaluate its effects on histone methylation and gene expression. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar). Histone H3K4 methylation levels are assessed by Western blotting or mass spectrometry. Gene expression changes are analyzed by qPCR or RNA sequencing. Cell viability, proliferation, and apoptosis are assessed using standard assays. The compound's effects on SMYD3-dependent cellular processes are further investigated.
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| Animal Protocol |
For in vivo animal experiments, SMYD3-IN-1 can be administered to animals via various routes including oral gavage, intravenous injection, or intraperitoneal injection, depending on its solubility and pharmacokinetic properties. The compound's efficacy can be evaluated in tumor models where SMYD3 is overexpressed or in other disease models where SMYD3 plays a role. Typical dosing regimens may range from 1 to 50 mg/kg administered daily or intermittently. Pharmacodynamic markers such as histone H3K4 methylation levels are measured in tissues. Tumor volume, body weight, and overall health are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SMYD3-IN-1 are not extensively detailed in the public literature. As a small molecule with a molecular weight of 507.02 g/mol, it may have reasonable oral bioavailability and tissue distribution. The presence of chlorine may influence its metabolic stability and clearance. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's protein binding, metabolism, and excretion pathways remain to be fully characterized. Formulation development may be necessary for optimal in vivo administration.
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| Toxicity/Toxicokinetics |
Toxicological data for SMYD3-IN-1 are limited, as it is primarily a research tool. As an irreversible SMYD3 inhibitor, its toxicity would depend on the importance of SMYD3 for normal cellular function. SMYD3 is a histone methyltransferase involved in gene regulation, and its inhibition could have effects on chromatin structure and gene expression. Comprehensive toxicology studies would be needed for further development. Appropriate safety precautions should be taken when handling this compound, including the use of personal protective equipment and adherence to institutional safety guidelines.
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| References | |
| Additional Infomation |
SMYD3-IN-1 is a research compound used to study SMYD3 biology and evaluate SMYD3 as a therapeutic target. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is an irreversible and selective SMYD3 inhibitor with an IC₅0 of 11.7 nM that blocks SMYD3-mediated lysine methylation. It is a valuable tool for studying the role of SMYD3 in gene regulation and cancer.
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| Molecular Formula |
C28H31CLN4O3
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|---|---|
| Molecular Weight |
507.02
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| Exact Mass |
506.208
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| CAS # |
2095160-79-3
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| PubChem CID |
138911344
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| Appearance |
Solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
800
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C2C(N=C(C3C=CC(C4(CC4)N)=CC=3)C=1)=CC(=CC=2)C(N1CCN(C(=O)OCCC)[C@@H](C1)C)=O
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| InChi Key |
ROAYRCZOBGZZPK-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C28H31ClN4O3/c1-3-14-36-27(35)33-13-12-32(17-18(33)2)26(34)20-6-9-22-23(29)16-24(31-25(22)15-20)19-4-7-21(8-5-19)28(30)10-11-28/h4-9,15-16,18H,3,10-14,17,30H2,1-2H3/t18-/m1/s1
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| Chemical Name |
propyl (2R)-4-[2-[4-(1-aminocyclopropyl)phenyl]-4-chloroquinoline-7-carbonyl]-2-methylpiperazine-1-carboxylate
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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 (~197.23 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 | 1.9723 mL | 9.8615 mL | 19.7231 mL | |
| 5 mM | 0.3945 mL | 1.9723 mL | 3.9446 mL | |
| 10 mM | 0.1972 mL | 0.9862 mL | 1.9723 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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