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| 25mg |
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Purity: ≥98%
Smurf1-IN-A01 is a novel, potent, high affinity and selective inhibitor of E3 ubiquitin-protein ligase Smurf1 (Smad ubiquitination regulatory factor-1) with Kd value of 3.7 nM. It disturbs Smurf1-Smad1/5 interaction and blocks Smurf1 mediated Smad1/5 ubiquitination. Smurf1-IN-A01 increases responsiveness to BMP-2 in myoblasts and osteoblasts. The ubiquitin ligase Smad ubiquitination regulatory factor-1 (Smurf1) negatively regulates bone morphogenetic protein (BMP) pathway by ubiquitinating certain signal components for degradation. Thus, it can be an eligible pharmacological target for increasing BMP signal responsiveness.
| Targets |
Smurf1(Kd= 3.664 nM)
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|---|---|
| ln Vitro |
In RAW264.7 cells stimulated by β-amylase, Smurf1-IN-A01 (10 μM, 30-60 min) foamy c-type lectin receptor 2d-mediated degradation of MyD88 [1]. In C3H10T1/2 cells, Smurf1-IN-A01 (10 μM, 24 h) decreases ALP activity and increases alizarin red staining [2]. In MCF-7 and T47D cells, Smurf1-IN-A01 (10 μM, 12 h) decreases ERα protein and ERE luciferase activity [3].
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| ln Vivo |
In degeneration models, Smurf1-IN-A01 (10 μM, 2 μL, intravitreal microinjection, single-body medication) can amplify early damage [4].
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| Animal Protocol |
Animal/Disease Models: Retinal degeneration model mouse [4]
Doses: 10 μM, 2μL Route of Administration: Injection into the vitreous cavity through a micro syringe. Experimental Results: Reduction of drusen-like spots. Resulting in a wider and straighter outer core layer. Resulting in the disappearance of the inner and outer segment hinges of photoreceptor cells. Downregulates NLRP3 and inhibits IL-1β. Can reduce NaIO3 retinal death. |
| References |
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| Molecular Formula |
C22H20CLF3N4O3S
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|---|---|
| Molecular Weight |
512.932413101196
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| Exact Mass |
512.089
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| Elemental Analysis |
C, 51.52; H, 3.93; Cl, 6.91; F, 11.11; N, 10.92; O, 9.36; S, 6.25
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| CAS # |
1007647-73-5
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| PubChem CID |
17555704
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
642.3±65.0 °C at 760 mmHg
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| Flash Point |
342.2±34.3 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.627
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| LogP |
3.87
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| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
34
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| Complexity |
824
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1C(F)(F)F)S(N1CCN(C(C2C=CC(=CC=2)N2C(C)=CC=N2)=O)CC1)(=O)=O
|
| InChi Key |
QFYLTUDRXBNZFQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20ClF3N4O3S/c1-15-8-9-27-30(15)17-4-2-16(3-5-17)21(31)28-10-12-29(13-11-28)34(32,33)18-6-7-20(23)19(14-18)22(24,25)26/h2-9,14H,10-13H2,1H3
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| Chemical Name |
[4-[[4-Chloro-3-(trifluoromethyl)phenyl]sulfonyl]-1-piperazinyl][4-(5-methyl-1H-pyrazol-1-yl)phenyl]-methanone
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| Synonyms |
Smurf1 inhibitor A01; Smurf1-IN-A01; Smurf1-inhibitor-A01; Smurf1INA01; Smurf1 IN A01;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : 62.5~100 mg/mL ( 121.85~194.95 mM )
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.06 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 20.8 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 | 1.9496 mL | 9.7479 mL | 19.4958 mL | |
| 5 mM | 0.3899 mL | 1.9496 mL | 3.8992 mL | |
| 10 mM | 0.1950 mL | 0.9748 mL | 1.9496 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.
 Primary selection of potential bio-active compounds.(a) Determination of the efficacy of various selected compounds of enhancing BMP induced ALP activity.(b) Chemical structures of A01 and A17.Sci Rep.2014 May 14;4:4965. |
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 Selective compounds stabilize Smad1/5 protein level.Sci Rep.2014 May 14;4:4965. |
 Selective compounds impair Smurf1-mediated Smad1/5 degradation.Sci Rep.2014 May 14;4:4965. |
 Selective compounds enhance BMP-2 signaling responsiveness.
Predicted binding modes of selective compounds to the defined pocket.Sci Rep.2014 May 14;4:4965. |
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 Selective compounds potentiate BMP-2 induced osteoblastic activity.Sci Rep.2014 May 14;4:4965. |
 Binding pocket definition andin silicoscreening.a) Refined structure of the Smurf1 WW1 domain bound to the diphosphorylated (pS210/pS214) region of the Smad1 linker. (b) Refined structure of the Smurf1 WW1 domain bound to the monophosphorylated (pS214) region of the Smad1 linker. (c) Receptor model of the Smurf1 WW1 domain (multiple colored) and diphosphorylated (pS210/pS214) region of the Smad1 linker (yellow). (d) Workflow ofin silicoscreening. |
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