| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
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| Targets |
Phosphodiesterase type 5 (PDE5) (IC50 = 0.64 μM)
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| ln Vitro |
Kuraridine exhibits strong inhibitory action (IC50=0.64 μM) against cGMP PDE5, with selectivity over PDE3 and PDE4 being 2.0 and 12.9 times, respectively[1]. In the absence of GABA, kuraridine causes significant inward currents of chlorides. 10% of the maximum IGABA generated by a saturating GABA concentration (1 mM) is not exceeded by the currents[2]. Kuraridine causes concentration–response curves in Xenopus oocytes expressing GABAA receptors made up of α1, β2, and γ2S subunits, resulting in an increase in IGABA (EC50=4.0±2.4 μM)[2].
During the search for naturally occurring cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) inhibitors, it was found that the extracts from Sophora flavescens exhibit potent inhibitory activity against cGMP PDE5 prepared from rat diaphragm. Therefore, the inhibitory activities of five flavonoids, kushenol H (1), kushenol K (2), kurarinol (3), sophoflavescenol (4) and kuraridine (5), isolated from S. flavescens were measured against cGMP PDE5 to identify potent cGMP PDE5 inhibitory constituents. Among tested compounds, sophoflavescenol (4), a C-8 prenylated flavonol, showed the most potent inhibitory activity (IC(50)=0.013 microM) against cGMP PDE5 with 31.5- and 196.2-fold selectivity over PDE3 and PDE4, respectively. Kinetic analysis revealed that sophoflavescenol was a mixed inhibitor of PDE5 with a K(i) value of 0.005 microM [1]. |
| Enzyme Assay |
Expression of GABAA receptors [2]
Stage V–VI oocytes from Xenopus laevis were prepared and cRNA was injected as previously described by Khom et al. Female X. laevis were anesthetized by exposing them for 15 min to a 0.2% MS-222 (methanesulfonate salt of 3-aminobenzoic acid ethyl) solution before surgically removing parts of the ovaries. Follicle membranes from isolated oocytes were enzymatically digested with 2 mg/mL collagenase. Synthesis of capped run-off poly(A+) cRNA transcripts was obtained from linearized cDNA templates (pCMV vector). One day after enzymatic isolation, the oocytes were injected with 50 nL of DEPC-treated water containing different cRNAs at a concentration of approximately 300–3000 pg/nL per subunit. To ensure expression of α1β2γ2S receptors, rat cRNA of α1,β2, and γ2S subunits were mixed in a 1:1:10 ratio. The amount of injected cRNA mixture was determined by means of a NanoDrop ND-1000. Oocytes were then stored at 18 °C in ND96 solution (90mM NaCl, 1mM KCl, 1mM MgCl2, 1 mM CaCl2, and 5 mM HEPES; pH 7.4) Voltage clamp measurements were performed between days 1 and 5 after cRNA injection. Two-microelectrode voltage clamp studies [2] Electrophysiological experiments were performed by the two-microelectrode voltage clamp method making use of a TURBO TEC-03X amplifier at a holding potential of −70 mV and pCLAMP 10 data acquisition software. Currents were low-pass-filtered at 1 kHz and sampled at 3 kHz. ND 96 solution was used as bath solution. The electrode filling solution consisted of 2 M KCl. Oocytes with maximal current amplitudes >3 μA were discarded to exclude voltage clamp errors. Before application of test solutions, a dose–response experiment with GABA concentrations ranging from 0.1 to 1 mM was performed to determine GABA EC3–10 (typically between 3 and 10 μM). |
| References |
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| Additional Infomation |
Kuraridin has been reported in Sophora flavescens with data available.
An EtOAc extract from the roots of Sophora flavescens (Kushen) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes transiently expressing GABA(A) receptors with subunit composition, α (1) β (2) γ (2S). HPLC-based activity profiling of the extract led to the identification of 8-lavandulyl flavonoids, kushenol I, sophoraflavanone G, (-)-kurarinone, and kuraridine as GABA(A) receptor modulators. In addition, a series of inactive structurally related flavonoids were characterized. Among these, kushenol Y (4) was identified as a new natural product. The 8-lavandulyl flavonoids are first representatives of a novel scaffold for the target.[2] |
| Molecular Formula |
C26H30O6
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|---|---|
| Molecular Weight |
438.51
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| Exact Mass |
438.204
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| Elemental Analysis |
C, 71.21; H, 6.90; O, 21.89
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| CAS # |
34981-25-4
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| PubChem CID |
44428631
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| Appearance |
White to yellow solid powder
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| LogP |
5.504
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
694
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(=CC[C@H](CC1=C(C(=C(C=C1O)OC)C(=O)/C=C/C2=C(C=C(C=C2)O)O)O)C(=C)C)C
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| InChi Key |
PIAPWPAWQGDOMN-SXAWMYDMSA-N
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| InChi Code |
InChI=1S/C26H30O6/c1-15(2)6-7-18(16(3)4)12-20-23(30)14-24(32-5)25(26(20)31)21(28)11-9-17-8-10-19(27)13-22(17)29/h6,8-11,13-14,18,27,29-31H,3,7,12H2,1-2,4-5H3/b11-9+/t18-/m1/s1
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| Chemical Name |
(E)-1-[2,4-dihydroxy-6-methoxy-3-[(2R)-5-methyl-2-prop-1-en-2-ylhex-4-enyl]phenyl]-3-(2,4-dihydroxyphenyl)prop-2-en-1-one
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| Synonyms |
34981-25-4; KURAIDIN; kuraridin; (E)-1-[2,4-dihydroxy-6-methoxy-3-[(2R)-5-methyl-2-prop-1-en-2-ylhex-4-enyl]phenyl]-3-(2,4-dihydroxyphenyl)prop-2-en-1-one; (E)-1-(2,4-dihydroxy-6-methoxy-3-((2R)-5-methyl-2-prop-1-en-2-ylhex-4-enyl)phenyl)-3-(2,4-dihydroxyphenyl)prop-2-en-1-one; CHEMBL243362; Z399B8AG6Z;
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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 (228.04 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 | 2.2804 mL | 11.4022 mL | 22.8045 mL | |
| 5 mM | 0.4561 mL | 2.2804 mL | 4.5609 mL | |
| 10 mM | 0.2280 mL | 1.1402 mL | 2.2804 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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