LMK-235 - HDAC 抑制劑 - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELMK-235Cat. No.: HY-18998CAS No.: 1418033-25-6分式: CHNO分量: 294.35作靶點: HDAC作通路: Cell Cycle/DNA Damage; Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 30 mg/mL (101.92 mM)* means s

2、oluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 3.3973 mL 16.9866 mL 33.9732 mL5 mM 0.6795 mL 3.3973 mL 6.7946 mL10 mM 0.3397 mL 1.6987 mL 3.3973 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 LMK-235種有效的，選擇性的 HDAC4/5 抑制劑，可抑制HDAC5，HDAC4，HDAC6，H

3、DAC1，HDAC2，HDAC11 和 HDAC8 的活性，IC50 值分別為 4.22 nM，11.9nM，55.7 nM，320 nM，881 nM，852 nM 和 1278 nM，可于癌癥研究。IC50 & Target HDAC5 HDAC4 HDAC6 HDAC14.22 nM (IC50) 11.9 nM (IC50) 55.7 nM (IC50) 320 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEHDAC11 HDAC2 HDAC8852 nM (IC50) 881 nM (IC50) 1278 nM (

4、IC50)體外研究 LMK-235 shows cytotoxic activity against human ovarian cancer cell lines A2780 and A2780 CisR, withIC50s of 0.49 M and 0.32 M, respectively. LMK-235 inhibits HDAC in A2780 and A2780 CisR cell lines,with IC50s of 0.65 M and 0.32 M, respectively. LMK-235 produces a higher reduction in cell v

5、iability incomparison to the combination of cisplatin and vorinostat in all cell lines 1. LMK-235 (0, 0.625, 1.25, 2.5, 5,10, and 20 M) reduces the proliferation of BC cells in a dose- and time-dependent manner. LMK-235 (0-800nM) also inhibits the growth of BC cells. Moreover, LMK-235 synergizes wit

6、h bortezomib in BC cell lines 2.LMK235 (2, 20nM) decreases in HDAC4 nuclear accumulation in Cdkl5 -/Y NPCs, completely restores thereduced number of neurons generated from Cdkl5 -/Y NPCs. LMK235 also restores histone 3 acetylation inCdkl5 -/Y NPCs. LMK235 causes a notable increase in the isoform IV,

7、 but does not affect BDNF isoforms I orII 3.體內(nèi)研究 LMK235 (5 and 20mg/kg) restores survival and maturation of postmitotic granule neurons in Cdkl5 -/Y mice.LMK235 also restores synapse development in the dentate gyrus and hippocampus of Cdkl5 -/Y mice.Furthermore, LMK235 restores hippocampus-dependent

8、 learning and memory in Cdkl5 -/Y mice 3.PROTOCOLCell Assay 1 The rate of cell survival under the action of test substances is evaluated by an improved MTT assay. Theassay is based on the ability of viable cells to metabolize yellow 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)

9、to violet formazan that can be detected spectrophotometrically. In brief,A2780, Cal27, Kyse510, and MDA-MB-231 cell lines are seeded at a density of 5000, 7000, 8000, and 10000 cells/well in 96-well plates. After 24 h, cells are exposed to increased concentrations of the testcompounds. Incubation is

10、 ended after 72 h, and cell survival is determined by addition of MTT solution (5mg/mL in phosphate buffered saline). The formazan precipitate is dissolved in DMSO. Absorbance ismeasured at 544 and 690 nm in a FLUOstar microplate reader 1.MCE has not independently confirmed the accuracy of these met

11、hods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 J Mol Med (Berl). 2019 Jun 14. Life Sci. 2019 Apr 15;223:146-157. Life Sci. 2018 Aug 15;207:386-394. Exp Cell Res. 2018 Dec 15;373(1-2):211-220. Cancer Biol Ther. 2018;19(9):825-834.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 M

12、aster of Small Molecules 您邊的抑制劑師www.MedChemE1. Marek L, et al. Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4and HDAC5 with improved activity against chemoresistant cancer cells. J Med Chem. 2013 Jan 24;56(2):427-36.2. Li A, et

13、 al. HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in humanbreast cancer. Oncotarget. 2016 Jun 21;7(25):37966-37978.3. Trazzi S, et al. HDAC4: a key factor underlying brain developmental alterations in CDKL5 disorder. Hum Mol Genet. 2016 Sep15;25(18):3887-3907.McePdf