LMK-235

LMK-235CAS号: 1418033-25-6分子式: C15H22N2O4分子量: 294.35描述纯度储存/保存方法别名可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)

产品描述
描述

LMK-235 is a selective histone deacetylase (HDAC) 4 and HDAC5 inhibitor.

纯度
>98%
储存/保存方法
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
基本信息
别名
LMK235, LMK 235
可溶性/溶解性
DMSO: ≥ 30 mg/mL
生物活性
靶点
HDAC
In vitro(体外研究)
LMK-235 shows cytotoxic activity against human ovarian cancer cell lines A2780 and A2780 CisR, with IC50s of 0.49 μM and 0.32 μM, respectively. LMK-235 inhibits HDAC in A2780 and A2780 CisR cell lines, with IC50s of 0.65 μM and 0.32 μM, respectively. LMK-235 produces a higher reduction in cell viability in comparison to the combination of cisplatin and vorinostat in all cell lines. LMK-235 (0, 0.625, 1.25, 2.5, 5, 10, and 20 μM) reduces the proliferation of BC cells in a dose- and time-dependent manner. LMK-235 (0-800 nM) also inhibits the growth of BC cells. Moreover, LMK-235 synergizes with bortezomib in BC cell lines. LMK235 (2, 20 nM) decreases in HDAC4 nuclear accumulation in Cdkl5 -/Y NPCs, completely restores the reduced number of neurons generated from Cdkl5 -/Y NPCs. LMK235 also restores histone 3 acetylation in Cdkl5 -/Y NPCs. LMK235 causes a notable increase in the isoform IV, but does not affect BDNF isoforms I or II.
In vivo(体内研究)
LMK235 (5 and 20 mg/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 learning and memory in Cdkl5 -/Y mice.

分子结构图

LMK-235

LMK-235

LMK-235

货号:
IL1520

品牌:
Jinpan

LMK-235

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产品简介
EC EINECS 808-770-7
别名 N-[[6-(羟基氨基)-6-氧代己基]氧基]-3,5-二甲基-苯甲酰胺
CAS 1418033-25-6
分子式 C15H22N2O4
分子量 294.35
储存条件 2-8℃
纯度 ≥98%
单位
生物活性 LMK-235 是一种有效的,选择性的 HDAC4/5 抑制剂,可抑制 HDAC5,HDAC4,HDAC6,HDAC1,HDAC2,HDAC11 和 HDAC8 的活性,IC50 值分别为 4.22 nM,11.9 nM,55.7 nM,320 nM,881 nM,852 nM 和 1278 nM,可用于癌症研究。[1-3]
IC50 HDAC5:4.22 nM ; HDAC4:11.9 nM [1-3]
In Vitro LMK-235显示针对人卵巢癌细胞系A2780和A2780 CisR的细胞毒活性,IC50分别为0.49μM和0.32μM。 LMK-235抑制A2780和A2780 CisR细胞系中的HDAC,IC50分别为0.65μM和0.32μM。与顺铂和伏立诺他在所有细胞系中的组合相比,LMK-235产生更高的细胞活力降低[1]。 LMK-235(0,0.625,1.25,2.5,5,10和20μM)以剂量和时间依赖性方式减少BC细胞的增殖。 LMK-235(0-800nM)也抑制BC细胞的生长。此外,LMK-235与BC细胞系中的硼替佐米协同作用[2]。 LMK235(2,20 nM)在Cdkl5 – /Y NPC中HDAC4核积累减少,完全恢复由Cdk15 – /Y NPC产生的神经元数量减少。 LMK235还恢复了Cdkl5 – /Y NPC中的组蛋白3乙酰化。 LMK235引起同种型IV显著增加,但不影响BDNF同种型I或II [3]。
In Vivo LMK235(5和20 mg/kg)恢复Cdkl5 – /Y小鼠中有丝分裂后颗粒神经元的存活和成熟。 LMK235还可恢复Cdkl5 – /Y小鼠齿状回和海马中的突触发育。此外,LMK235恢复Cdkl5 – /Y小鼠的海马依赖性学习和记忆[3]。
SMILES O=C(NOCCCCCC(NO)=O)C1=CC(C)=CC(C)=C1
靶点 HDAC
细胞实验 通过改进的MTT测定评估测试物质作用下的细胞存活率。该测定基于活细胞将黄色3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)代谢成紫色甲烷的能力,其可以通过分光光度法检测。简言之,将A2780,Cal27,Kyse510和MDA-MB-231细胞系以5000,7000,8000和10000个细胞/孔的密度接种在96孔板中。 24小时后,将细胞暴露于浓度增加的试验化合物。 72小时后终止孵育,并通过添加MTT溶液(在磷酸盐缓冲盐水中5mg/mL)测定细胞存活。将甲crystals沉淀物溶解在DMSO中。在FLUOstar酶标仪[1]中测量544和690 nm处的吸光度。
数据来源文献 [1]. Marek L, et al. Histone deacetylase (HDAC) inhibitors with a novel connecting unit linker region reveal a selectivity profile for HDAC4 and HDAC5 with improved activity against chemoresistant cancer cells. J Med Chem. 2013 Jan 24;56(2):427-36.
[2]. Li A, et al. HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast 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 Sep 15;25(18):3887-3907.
规格 5mg 10mg 25mg

LMK-235是HDAC4和HDAC5的选择性抑制剂。