1338247-35-0
1338247-35-0 structure
- Name: LIMKi 3
- Chemical Name: N-{5-[1-(2,6-Dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-5-yl]- 1,3-thiazol-2-yl}-2-methylpropanamide
- CAS Number: 1338247-35-0
- Molecular Formula: C17H14Cl2F2N4OS
- Molecular Weight: 431.287
- Catalog: Signaling Pathways Cell Cycle/DNA Damage LIM Kinase (LIMK)
- Create Date: 2016-08-31 10:49:14
- Modify Date: 2024-01-13 21:09:34
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BMS-5 is a potent LIMK inhibitor with IC50s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively.
| Name | N-{5-[1-(2,6-Dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-5-yl]- 1,3-thiazol-2-yl}-2-methylpropanamide |
|---|---|
| Synonyms |
N-{5-[1-(2,6-Dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-5-yl]-1,3-thiazol-2-yl}-2-methylpropanamide
Propanamide, N-[5-[1-(2,6-dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-5-yl]-2-thiazolyl]-2-methyl- BMS-5 |
| Description | BMS-5 is a potent LIMK inhibitor with IC50s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively. |
|---|---|
| Related Catalog | |
| Target |
LIMK1:7 nM (IC50) LIMK2:8 nM (IC50) |
| In Vitro | BMS-5 inhibits cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 mouse Schwann cells (MSCs) with an IC50 of ~2 µM. BMS-5 reduces Nf2ΔEx2 MSC viability in a dose-dependent manner with an IC50 of 3.9 µM, but does not significantly reduce the viability of control Nf2flox2/flox2 MSCs at equivalent BMS-5 concentrations. At 10 µM BMS-5, Nf2ΔEx2 MSC viability is 40% compared to 83% for controls[2]. |
| In Vivo | BMS-5 (20 or 200 μM/side) is bilaterally infused into the hippocampus of rats immediately after contextual fear conditioning training. Rats are tested for memory consolidation 48 h after fear conditioning. Post hoc analysis shows that the group treated with 200 μM BMS-5 express lower freezing levels compared to the 20 μM and vehicle groups (P<0.01)[3]. |
| Kinase Assay | The protein kinase domains of human LIMK1 and LIMK2 are expressed as glutathione S-transferase fusion proteins using the Bac-to-Bac system in Sf9 cells. Compounds 1 to 6 (e.g., BMS-5) are assayed for inhibition of LIMK1 and LIMK2 protein kinase activity by radioactive phosphate incorporation into biotinylated full-length human destrin. Reactions are done with a concentration series of compound in 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). Reactions are terminated by addition of 140 μL of 20% TCA/100 mM sodium pyrophosphate, and the precipitates are harvested onto GF/C unifilter plates. The radioactivity incorporated is determined using a TopCount after addition of 35 μL Microscint scintillation fluid[1]. |
| Cell Assay | Cell membrane asymmetry is measured. Nf2ΔEx2 MSCs plated in a 6-well format are incubated with 2 µM BMS-5 or DMSO vehicle for 24 hrs. Cell are harvested and assayed. Plasma membrane asymmetry is evaluated with the Violet ratiometric assay by flow cytometry[2]. |
| Animal Admin | Rats [3] Male Wistar rats (age 2-3 months, weight 290-350 g) are used. BMS-5 is prepared in a vehicle solution (1% DMSO in sterile isotonic saline). At the time of infusion, a 30-gauge infusion needle is fitted into a guide cannula, with its tip protruding 1.0 mm beyond the guide cannula end and aimed at the pyramidal cell layer of CA1 of the dorsal hippocampus. Avolume of 1 μL of BMS-5 (20 and 200 μM) or vehicle (DMSO 1%) is bilaterally infused in a time of 90 s. The doses of BMS-5 are based on its IC50 value and in vitro studies. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Molecular Formula | C17H14Cl2F2N4OS |
| Molecular Weight | 431.287 |
| Exact Mass | 430.023346 |
| PSA | 91.54000 |
| LogP | 5.97 |
| Index of Refraction | 1.662 |
| Storage condition | 2-8℃ |