| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
hCyh1 (IC50 = 5.4 μM); hCyh2 (IC50 = 2.4 μM); mCyh3 (IC50 = 5.4 μM); hCyh3 (IC50 = 5.6 μM); drosophila steppke (IC50 = 5.6 μM); yGea2-S7 (IC50 = 65 μM)
SecinH3 targets the cytohesin family of small GEFs by binding to their Sec7 domain. It also inhibits Sec23, a key component of the COPII vesicle coat, and the small GTPase ARF6. By inhibiting these targets, it disrupts intracellular protein trafficking and signaling pathways. It has an IC50 of 2.2 µM for blocking IGFBP1 transcriptional repression caused by insulin. |
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| ln Vitro |
SecinH3 is a small GEF inhibitor that prefers the cytohesin family of small GEFs and is specific for the Sec7 family. IGFBP1 transcriptional repression caused by insulin is almost entirely blocked by SecinH3 with an IC50 of 2.2 M. Additionally, SecinH3 prevents insulin from stimulating ARF6 to move to the plasma membrane. It is discovered that, in a concentration-dependent manner, SecinH3 prevents the insulin-dependent phosphorylation of Akt and FoxO1A. SecinH3 entirely prevents the insulin-induced exclusion of FoxO1A from the nucleus. Additionally, SecinH3[1] inhibits IRS1's ability to bind to the insulin receptor.
In vitro, SecinH3 acts as a cytohesin antagonist and inhibits Sec23 and ARF6. It blocks IGFBP1 transcriptional repression caused by insulin with an IC50 of 2.2 µM. These activities have been demonstrated in cell-based assays, where it disrupts intracellular protein trafficking and modulates cellular signaling pathways. |
| ln Vivo |
In mice treated with SecinH3, as opposed to mice fed the same diet without SecinH3, the expression levels of the insulin-repressed gluconeogenic genes are increased, while the expression levels of the insulin-induced glycolytic genes are decreased. Mice treated with SecinH3 also exhibit an inhibition of the Akt phosphorylation induced by insulin. Carnitine palmitoyltransferase 1a (Cpt1a) and hydroxyacyl-CoA dehydrogenase (Hadha), two essential mitochondrial -oxidation enzymes whose expression is suppressed by insulin, are expressed more frequently in the mice treated with SecinH3. In mice treated with SecinH3, serum insulin levels were found to be significantly higher and glucose levels to be slightly elevated. The serum of mice treated with SecinH3 consequently contains more 3-hydroxybutyrate[1].
In vivo, SecinH3 has been studied for its potential therapeutic applications in targeting cancer and other diseases by modulating cellular trafficking and inhibiting the growth of tumor cells. However, specific details of in vivo efficacy studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use. |
| Enzyme Assay |
A library of small molecules (10000 molecules) from Comgenex was screened in duplicate in 386 well plates using fluorescence polarization at 485 nm for excitation and 520 nm for read-out in a reaction volume of 50 μL at 37 °C. PBS, pH 7.5, 3 mM MgCl2, 100 nM fluorescein-labeled M69 aptamer, and 1 μM cytohesin-1 Sec7 at 100 μM compound concentrations make up the screening buffer.
The in vitro binding/functional assay for SecinH3 measures its ability to inhibit cytohesin GEF activity. These cell-free assays use purified cytohesin proteins and measure the exchange of GDP for GTP on ARF GTPases. The compound's inhibitory potency (IC50) is determined by measuring the reduction in GEF activity. Its effects on Sec23 and ARF6 can be assessed using similar assays. |
| Cell Assay |
In 12 well plates with 105 HepG2 cells seeded inside, 10% FCS-containing EMEM is used for a 24-hour culture. After 24 hours of serum starvation in EMEM, cells are stimulated for 12 hours with 10 nM insulin in the presence of SecinH3, D5 (a negative control), or vehicle (0.2% final DMSO concentration). To prepare total mRNA, a kit is used, and 1 μg of RNA is used to produce cDNA for qPCR. Data are normalized to β2-microglobulin expression and qPCR is used to perform the analysis[1].
In vitro cellular assays for SecinH3 assess its effects on protein trafficking and signaling. Cells are treated with SecinH3, and the effects on COPII vesicle formation, ARF6 signaling, and gene expression are measured. Its ability to block IGFBP1 transcriptional repression is assessed by measuring IGFBP1 mRNA levels. These assays demonstrate the compound's functional activity in a relevant cellular context. |
| Animal Protocol |
In vivo animal studies for SecinH3 are conducted in models of cancer to evaluate its antitumor efficacy. However, specific details of these studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for SecinH3 are not extensively detailed in the available literature. As a small molecule, its pharmacokinetic properties would be important for its in vivo efficacy. However, specific parameters such as half-life and bioavailability are not provided. It is intended for research use only.
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| Toxicity/Toxicokinetics |
Specific toxicity data for SecinH3 are not extensively detailed in the available literature. As a cytohesin and ARF6 inhibitor, its toxicity profile is likely related to its mechanism of action. However, its potential for targeting cancer suggests a manageable safety profile. It is intended for research purposes only and is not for human use.
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| References | |
| Additional Infomation |
N-[4-[5-(1,3-benzodioxacyclopenten-5-yl)-3-methoxy-1,2,4-triazol-1-yl]phenyl]-2-(phenylthio)acetamide is a member of the triazole class of compounds.
SecinH3 (CAS 853625-60-2) is a selective cytohesin antagonist targeting the Sec7 domain of cytohesin GEFs. It also inhibits Sec23 and ARF6. It blocks IGFBP1 transcriptional repression with an IC50 of 2.2 µM. It has a molecular formula of C24H20N4O4S and a molecular weight of 460.51. It is a research compound and is not approved for clinical use. |
| Molecular Formula |
C24H20N4O4S
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|---|---|
| Molecular Weight |
460.5
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| Exact Mass |
460.12
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| Elemental Analysis |
C, 62.60; H, 4.38; N, 12.17; O, 13.90; S, 6.96
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| CAS # |
853625-60-2
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| Related CAS # |
853625-60-2
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| PubChem CID |
1029232
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.687
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| LogP |
4.94
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
644
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CSC1C=CC=CC=1)NC1C=CC(N2C(C3C=C4C(OCO4)=CC=3)=NC(OC)=N2)=CC=1
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| InChi Key |
QPGYAMIHXLCFTJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H20N4O4S/c1-30-24-26-23(16-7-12-20-21(13-16)32-15-31-20)28(27-24)18-10-8-17(9-11-18)25-22(29)14-33-19-5-3-2-4-6-19/h2-13H,14-15H2,1H3,(H,25,29)
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| Chemical Name |
N-[4-[5-(1,3-benzodioxol-5-yl)-3-methoxy-1,2,4-triazol-1-yl]phenyl]-2-phenylsulfanylacetamide
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| Synonyms |
Secin H3; SecinH3; Secin-H3
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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: 92~130 mg/mL(199.8~282.3 mM)
Ethanol (warmed with 50ºC water bath): ~1 mg/mL (~2.2 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (7.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1716 mL | 10.8578 mL | 21.7155 mL | |
| 5 mM | 0.4343 mL | 2.1716 mL | 4.3431 mL | |
| 10 mM | 0.2172 mL | 1.0858 mL | 2.1716 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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