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| 25mg |
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Purity: ≥98%
BMS-3 is a potent inhibitor of the LIM kinase (LIMK)with IC50 of 5nM and 6 nM for LIMK1 and LIMK2 respectively. Specific inhibitors (BMS-3) inhibiting LIMK1 led to reduced actin polymerization during capacitation and a sharp decline in the fraction of sperm undergoing acrosomal exocytosis. Thus, we were able to show that mouse sperm contain and function as the master regulators of actin dynamics in somatic cells for the first time. We have put forth a working model that explains how LIMK1 and Cofilin regulate acrosomal exocytosis in mouse sperm by combining the findings of this investigation with additional findings from the literature.
| Targets |
LIMK1 (IC50 = 5 nM); LIMK2 (IC50 = 6 nM)
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| ln Vitro |
BMS-3 (Compound 2) results in a dose-dependent decrease in the number of cells and, in A549 human lung cancer cells, induces mitotic arrest by raising the intensity of total nuclear DNA and the phosphorylation of histone H3 after a 24-hour treatment. A549 human lung cancer cells are inhibited by BMS-3 at an EC50 of 154 nM[1]. LIMK1's direct involvement in the phosphorylation of Cofilin is demonstrated using BMS-3. After incubating for 10 minutes in capacitating conditions, p-Cofilin decreases in a dose-dependent manner upon inhibition of p-LIMK with 1-50 μM of BMS-3. Sperm are also incubated for 10 minutes under non-capacitating conditions as a control, which produces low p-Cofilin levels. Actin polymerization levels are significantly lower in the presence of 1 or 50 μM of BMS-3 when compared to the control (DMSO) conditions. For 90 minutes, mouse sperm are cultured in capacitating conditions with or without increasing concentrations of p-LIMK inhibitor BMS-3 (0, 1, 10 and 50 μM). The proportion of sperm undergoing acrosomal exocytosis following stimulation with 20 μM of progesterone significantly decreases as BMS-3 concentrations rise[2].
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| ln Vivo |
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| Enzyme Assay |
In Sf9 cells, the Bac-to-Bac system is used to express the protein kinase domains of human LIMK1 and LIMK2 as glutathione S-transferase fusion proteins. Radioactive phosphate incorporation into biotinylated full-length human destrin is used to test compounds 1 through 6 (e.g., BMS-3) for their ability to inhibit LIMK1 and LIMK2 protein kinase activity. The following solutions are used for the reactions: 25 mM HEPES, 100 mM NaCl, 5 mM MgCl2, 5 mM MnCl2, 1 μM total ATP, 83 μg/mL biotinylated destrin, 167 ng/mL glutathione S-transferase-LIMK1, or 835 ng/mL glutathione S-transferase-LIMK2 in a total volume of 60 μL at room temperature for 30 min (LIMK1) or 60 min (LIMK2). The precipitates are collected onto GF/C unifilter plates after the reactions are stopped by adding 140 μL of 20% TCA/100 mM sodium pyrophosphate. Following the addition of 35 μL of Microscint scintillation fluid, the radioactivity incorporated is measured using a TopCount[1].
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| Cell Assay |
After a 24-hour treatment period in A549 human lung cancer cells, BMS-3 (Compound 2) results in a dose-dependent decrease in the number of cells and induces mitotic arrest through increases in total nuclear DNA intensity and histone H3 phosphorylation. BMS-3 inhibits human lung cancer cells A549, with an EC50 value of 154 nM.
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| Animal Protocol |
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| References |
| Molecular Formula |
C17H12CL2F2N4OS
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| Molecular Weight |
429.27
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| Exact Mass |
428.007
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| Elemental Analysis |
C, 47.57; H, 2.82; Cl, 16.52; F, 8.85; N, 13.05; O, 3.73; S, 7.47
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| CAS # |
1338247-30-5
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| Related CAS # |
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| PubChem CID |
73265272
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| Appearance |
White to off-white solid powder
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| Density |
1.7±0.1 g/cm3
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| Index of Refraction |
1.733
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| LogP |
5.46
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
549
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C([H])C([H])=C(C=1N1C(=C([H])C(C([H])(F)F)=N1)C1=C([H])N=C(N([H])C(C2([H])C([H])([H])C2([H])[H])=O)S1)Cl
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| InChi Key |
YBGGBHCJSAEIAS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12Cl2F2N4OS/c18-9-2-1-3-10(19)14(9)25-12(6-11(24-25)15(20)21)13-7-22-17(27-13)23-16(26)8-4-5-8/h1-3,6-8,15H,4-5H2,(H,22,23,26)
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| Chemical Name |
N-[5-[2-(2,6-dichlorophenyl)-5-(difluoromethyl)pyrazol-3-yl]-1,3-thiazol-2-yl]cyclopropanecarboxamide
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| Synonyms |
BMS-3; BMS3; BMS 3
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.82 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 25.0 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: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3295 mL | 11.6477 mL | 23.2954 mL | |
| 5 mM | 0.4659 mL | 2.3295 mL | 4.6591 mL | |
| 10 mM | 0.2330 mL | 1.1648 mL | 2.3295 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.
Inhibition of the active form of LIMK1 with a specific inhibitor results in a decrease of phosphorylated COFILIN on Ser3.Dev Biol.2015 Sep 15;405(2):237-49. |
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Inhibition of pLIMK1 produces a decrease in the capacitation-associated actin polymerization and in the percentage of sperm that undergo acrosomal exocytosis upon progesterone or calcium ionophore stimulation.Dev Biol.2015 Sep 15;405(2):237-49. |
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