BMS-5, a Potent LIM kinase inhibitor.

BMS-5 is a Potent LIM kinase inhibitor (IC50 values are 7 and 8 nM for LIMK1 and LIMK2 respectively). Inhibits cofilin phosphorylation in MDA-MB-231 breast cancer cells. Reduces MDA-MB-231 tumor cell invasion in a 3D matrigel invasion assay.

Product information

CAS Number: 1338247-35-0

Molecular Weight: 431.29

Formula: C17H14Cl2F2N4OS

Synonym:

LIMKI-3

LIMKI 3

LIMKI3

BMS-5

BMS 5

BMS5

Chemical Name: N-[5-[1-(2,6-Dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-5-yl]-2-thiazolyl]-2-methylpropanamide

Smiles: CC(C)C(=O)NC1=NC=C(S1)C1=CC(=NN1C1=C(Cl)C=CC=C1Cl)C(F)F

InChiKey: IVUGBSGLHRJSSP-UHFFFAOYSA-N

InChi: InChI=1S/C17H14Cl2F2N4OS/c1-8(2)16(26)23-17-22-7-13(27-17)12-6-11(15(20)21)24-25(12)14-9(18)4-3-5-10(14)19/h3-8,15H,1-2H3,(H,22,23,26)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

BMS-5 (LIMKi 3) inhibits cofilin-Ser3 phosphorylation in a dose-dependent manner in Nf2ΔEx2 mouse Schwann cells (MSCs) with an IC50 of ~2 µM. BMS-5 (LIMKi 3) 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.

In Vivo:

BMS-5 (LIMKi 3) (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).

References:

1. Wang W, Townes-Anderson E. LIM Kinase, a Newly Identified Regulator of Presynaptic Remodeling by Rod Photoreceptors After Injury. Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7847-58. doi: 10.1167/iovs.15-17278. PubMed PMID: 26658506; PubMed Central PMCID: PMC4682489.
2. Bao Z, Han X, Chen F, Jia X, Zhao J, Zhang C, Yong C, Tian S, Zhou X, Han L. Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells. BMC Microbiol. 2015 Aug 13;15:161. doi: 10.1186/s12866-015-0500-y. PubMed PMID: 26268695; PubMed Central PMCID: PMC4542120.
3. Park JB, Agnihotri S, Golbourn B, Bertrand KC, Luck A, Sabha N, Smith CA, Byron S, Zadeh G, Croul S, Berens M, Rutka JT. Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway. Oncotarget. 2014 Oct 15;5(19):9382-95. PubMed PMID: 25237832; PubMed Central PMCID: PMC4253441.
4. Petrilli A, Copik A, Posadas M, Chang LS, Welling DB, Giovannini M,Fernandez-Valle C. LIM domain kinases as potential therapeutic targets for neurofibromatosis type 2. Oncogene. 2014 Jul 3;33(27):3571-82. doi: 1038/onc.2013.320. Epub 2013 Aug 12. PubMed PMID: 23934191; PubMed Central PMCID: PMC4016185.

Products are for research use only. Not for human use.