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BMS-5

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Chemical Structure| 1338247-35-0 同义名 : LIMKi 3;LIM Kinase Inhibitor I
CAS号 : 1338247-35-0
货号 : A496357
分子式 : C17H14Cl2F2N4OS
纯度 : 99%+
分子量 : 431.287
MDL号 : MFCD17019327
存储条件:

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 35 mg/mL(81.15 mM),注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方:
生物活性
描述 LIMK1 and LIMK2 regulate the actin cytoskeleton by phosphorylating and inactivating the cofilin family of actin-depolymerizing factors; LIMK1 also acts to destabilize microtubules and regulates cell motility, including tumor metastasis[3]. BMS-5 is a potent LIMK inhibitor with IC50s of 7 nM and 8 nM for LIMK1 and LIMK2, respectively[3]. BMS-5 inhibits cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 mouse Schwann cells (MSCs) with an IC50 of ~2 µM, and it 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[4]. BMS-5 (20 or 200 μM/side) or vehicle 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 expresses lower freezing levels compared to the 20 μM and vehicle groups (P < 0.01). An additional experiment is performed in order to test if a short-term fear memory (STM) could be affected by LIMK inhibition. Animals are infused with 200 μM BMS-5 immediately after training and are tested in the same context 2 h later. No significant difference is found between both groups, BMS-5 and vehicle, in the test, suggesting that actin dynamics briefly after training is not crucial to STM expression[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.32mL

0.46mL

0.23mL

11.59mL

2.32mL

1.16mL

23.19mL

4.64mL

2.32mL

参考文献

[1]Petrilli A, Copik A, et al. LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2. Oncogene. 2014 Jul 3;33(27):3571-82.

[2]Ross-Macdonald P, de Silva H, et al. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008 Nov;7(11):3490-8.

[3]Ross-Macdonald P, de Silva H, Guo Q, Xiao H, Hung CY, Penhallow B, Markwalder J, He L, Attar RM, Lin TA, Seitz S, Tilford C, Wardwell-Swanson J, Jackson D. Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors. Mol Cancer Ther. 2008 Nov;7(11):3490-8. doi: 10.1158/1535-7163.MCT-08-0826. PMID: 19001433.

[4]Petrilli A, Copik A, Posadas M, Chang LS, Welling DB, Giovannini M, Fernández-Valle C. LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2. Oncogene. 2014 Jul 3;33(27):3571-82. doi: 10.1038/onc.2013.320. Epub 2013 Aug 12. PMID: 23934191; PMCID: PMC4016185.

[5]Lunardi P, Sachser RM, Sierra RO, Pedraza LK, Medina C, de la Fuente V, Romano A, Quillfeldt JA, de Oliveira Alvares L. Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction. Mol Neurobiol. 2018 Feb;55(2):958-967. doi: 10.1007/s12035-016-0361-x. Epub 2017 Jan 13. PMID: 28084590.