LMK 235
(Synonyms: N-[[6-(羟基氨基)-6-氧代己基]氧基]-3,5-二甲基-苯甲酰胺) 目录号 : GC13237
A selective inhibitor of HDAC4 and HDAC5
Cas No.:1418033-25-6
Sample solution is provided at 25 µL, 10mM.
Description:
IC50: cytotoxicity IC50 (490 nm for A2780; 320 nm for A2780 CisR); HDAC inhibition (650 nM for A2780; 320 nm for A2780 CisR)
Histone deacetylases (EC 3.5.1.98, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. Histone deacetylase inhibitors (HDIs) have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics, for example, valproic acid. In more recent times, HDIs are being studied as a mitigator or treatment for neurodegenerative diseases.
In vitro: LMK235 showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC assay but enhanced cytotoxic effects against the human cancer cell lines A2780, Cal27, Kyse510, and MDA-MB231. LMK235 shows nanomolar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher micromolar range. In contrast to vorinostat, LMK235 showed a novel HDAC isoform selectivity profile with preference for HDAC4 and HDAC5, which are inhibited with low nanomolar IC50 values [1].
In vivo: In a mouse in-vivo study, synergistic inhibition was demonstrated for LMK235 and Cytarabine in proliferation assays and in colony formation assays. These findings demonstrate that in vivo RNAi screening for therapeutic efficacy is feasible. HDAC4 might be an important target to enhance efficacy of anti-leukemic drugs [2].
Clinical trial: LMK235 is currently in the preclinical development and no clinical trial is ongoing.
References:
[1] Marek L, Hamacher A, Hansen FK, Kuna K, Gohlke H, Kassack MU, Kurz T. 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;56(2):427-36.
[2] Stephanie Lettermann, Konstantin Agelopoulos, Christian Rohde, Beate Lindtner, Linda Marek, Georg Hempel, Matthias Stelljes, Wolfgang E. Berdel, Thomas Kurz and Carsten Müller-Tidow. In Vivo RNAi Screening Identifies HDAC4 As a Mediator Of Chemoresistance In Acute Myeloid Leukemia. 55th ASH Annual Meeting and Exposition (2013) (https://ash.confex.com/ash/2013/webprogram/Paper60036.html)
Cell experiment: | The rate of cell survival under the action of test substances is evaluated by an improved MTT assay. The assay is based on the ability of viable cells to metabolize yellow 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) 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 10 000 cells/well in 96-well plates. After 24 h, cells are exposed to increased concentrations of the test compounds. Incubation is ended after 72 h, and cell survival is determined by addition of MTT solution (5 mg/mL in phosphate buffered saline). The formazan precipitate is dissolved in DMSO. Absorbance is measured at 544 and 690 nm in a FLUOstar microplate reader[1]. |
References: [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. | |
| Cas No. | 1418033-25-6 | SDF | |
| 别名 | N-[[6-(羟基氨基)-6-氧代己基]氧基]-3,5-二甲基-苯甲酰胺 | ||
| 化学名 | N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide | ||
| Canonical SMILES | CC1=CC(C)=CC(C(NOCCCCCC(NO)=O)=O)=C1 | ||
| 分子式 | C15H22N2O4 | 分子量 | 294.35 |
| 溶解度 | ≥ 9.95mg/mL in DMSO, ≥ 53.8 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3973 mL | 16.9866 mL | 33.9732 mL |
| 5 mM | 0.6795 mL | 3.3973 mL | 6.7946 mL |
| 10 mM | 0.3397 mL | 1.6987 mL | 3.3973 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet