SW-100
目录号 : GC64968
SW-100 是一种有效的组蛋白脱乙酰基酶 6 (HDAC6) 抑制剂，IC50 值为 2.3 nM，相对于其他 HDAC 酶，对 HDAC6 的选择性至少高 1000倍。SW-100 显著提高了跨越血脑屏障的能力。
Cas No.:2126744-35-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
HDAC1 5.23μM(IC50) | HDAC2 32.8μM(IC50) | HDAC3 29.5μM(IC50) | HDAC4 10.9μM(IC50) | HDAC5 4.07μM(IC50) | HDAC6 2.3nM(IC50) | HDAC7 4.55μM(IC50) | HDAC8 3.72μM(IC50) | HDAC9 3.46μM(IC50) | HDAC10 26.2μM(IC50) | HDAC11 5.72μM(IC50) |
SW-100, a selective histone deacetylase 6 (HDAC6) inhibitor with an IC50 of 2.3 nM, shows at least 1000-fold selectivity for HDAC6 relative to all other HDAC isozymes. SW-100 displays a significantly improved ability to cross the blood-brain-barrier[1].
SW-100 (0.01-10 µM; 48 hours) shows obvious increase in the acetylated α-tubulin levels in a dose-dependent manner[1].
SW-100 (20 mg/kg; i.p.; twice a day for two days) ameliorates several memory and learning impairments including novel object recognition, temporal ordering, and coordinate and categorical spatial processing in mouse model of Fragile X syndrome[1].
[1]. Kozikowski AP, et al. Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and LearningImpairments in a Mouse Model of Fragile X Syndrome. ACS Chem Neurosci. 2019 Mar 20;10(3):1679-1695.
| Cas No. | 2126744-35-0 | SDF | Download SDF |
| 分子式 | C17H17ClN2O2 | 分子量 | 316.78 |
| 溶解度 | DMSO : ≥ 125 mg/mL (394.60 mM) | 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 | 3.1568 mL | 15.7838 mL | 31.5676 mL |
| 5 mM | 0.6314 mL | 3.1568 mL | 6.3135 mL |
| 10 mM | 0.3157 mL | 1.5784 mL | 3.1568 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。
Preclinical Evaluation of an 18F-Labeled SW-100 Derivative for PET Imaging of Histone Deacetylase 6 in the Brain
ACS Chem Neurosci 2021 Feb 17;12(4):746-755.PMID:33502174DOI:10.1021/acschemneuro.0c00774.
Histone deacetylase 6 (HDAC6), an enzyme involved in protein degradation, exhibits several unique properties, such as cytoplasmic localization and ubiquitin binding. HDAC6 has emerged as an interesting therapeutic target in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Techniques enabling noninvasive HDAC6 imaging in the brain could enhance understanding of its pathologic role, but development of brain-penetrating radioligands for HDACs imaging by positron emission tomography (PET) remains challenging. Here, we report the synthesis and evaluation of an 18F-labeled tetrahydroquinoline derivative, [18F]2, based on the HDAC6 selective inhibitor SW-100 as a brain HDAC6 imaging radioligand. [18F]2 was synthesized via copper-mediated radiofluorination from an arylboronic precursor, followed by removal of the catalyst by solid-phase extraction and then hydroxamic acid formation. [18F]2 demonstrated good penetration and moderate stability in the mouse brain. In mouse plasma, however, [18F]2 was rapidly metabolized to a corresponding carboxylic acid form. Blocking studies in mice with unlabeled compound 2 and HDAC6 selective inhibitors, including tubastatin A and ACY-775, demonstrated that the HDAC6 inhibitors displaced over 80% of [18F]2 taken up in the brain, indicating selective binding of [18F]2. These results suggest that [18F]2 is a potentially useful PET radioligand for brain HDAC6 imaging.
Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome
ACS Chem Neurosci 2019 Mar 20;10(3):1679-1695.PMID:30511829DOI:10.1021/acschemneuro.8b00600.
Disease-modifying therapies are needed for Fragile X Syndrome (FXS), as at present there are no effective treatments or cures. Herein, we report on a tetrahydroquinoline-based selective histone deacetylase 6 (HDAC6) inhibitor SW-100, its pharmacological and ADMET properties, and its ability to improve upon memory performance in a mouse model of FXS, Fmr1-/- mice. This small molecule demonstrates good brain penetrance, low-nanomolar potency for the inhibition of HDAC6 (IC50 = 2.3 nM), with at least a thousand-fold selectivity over all other class I, II, and IV HDAC isoforms. Moreover, through its inhibition of the α-tubulin deacetylase domain of HDAC6 (CD2), in cells SW-100 upregulates α-tubulin acetylation with no effect on histone acetylation and selectively restores the impaired acetylated α-tubulin levels in the hippocampus of Fmr1-/- mice. Lastly, SW-100 ameliorates several memory and learning impairments in Fmr1-/- mice, thus modeling the intellectual deficiencies associated with FXS, and hence providing a strong rationale for pursuing HDAC6-based therapies for the treatment of this rare disease.
Tetrahydroquinoline-Capped Histone Deacetylase 6 Inhibitor SW-101 Ameliorates Pathological Phenotypes in a Charcot-Marie-Tooth Type 2A Mouse Model
J Med Chem 2021 Apr 22;64(8):4810-4840.PMID:33830764DOI:10.1021/acs.jmedchem.0c02210.
Histone deacetylase 6 (HDAC6) is a promising therapeutic target for the treatment of neurodegenerative disorders. SW-100 (1a), a phenylhydroxamate-based HDAC6 inhibitor (HDAC6i) bearing a tetrahydroquinoline (THQ) capping group, is a highly potent and selective HDAC6i that was shown to be effective in mouse models of Fragile X syndrome and Charcot-Marie-Tooth disease type 2A (CMT2A). In this study, we report the discovery of a new THQ-capped HDAC6i, termed SW-101 (1s), that possesses excellent HDAC6 potency and selectivity, together with markedly improved metabolic stability and druglike properties compared to SW-100 (1a). X-ray crystallography data reveal the molecular basis of HDAC6 inhibition by SW-101 (1s). Importantly, we demonstrate that SW-101 (1s) treatment elevates the impaired level of acetylated α-tubulin in the distal sciatic nerve, counteracts progressive motor dysfunction, and ameliorates neuropathic symptoms in a CMT2A mouse model bearing mutant MFN2. Taken together, these results bode well for the further development of SW-101 (1s) as a disease-modifying HDAC6i.
HDAC6 inhibition promotes α-tubulin acetylation and ameliorates CMT2A peripheral neuropathy in mice
Exp Neurol 2020 Jun;328:113281.PMID:32147437DOI:10.1016/j.expneurol.2020.113281.
Charcot-Marie-Tooth type 2A (CMT2A) peripheral neuropathy, the most common axonal form of CMT, is caused by dominantly inherited point mutations in the Mitofusin 2 (Mfn2) gene. It is characterized by progressive length-dependent degeneration of motor and sensory nerves with corresponding clinical features of motor and sensory impairment. There is no cure for CMT, and therapeutic approaches are limited to physical therapy, orthopedic devices, surgery, and analgesics. In this study we focus on histone deacetylase 6 (HDAC6) as a therapeutic target in a mouse model of mutant MFN2 (MFN2R94Q)-induced CMT2A. We report that these mice display progressive motor and sensory dysfunction as well as a significant decrease in α-tubulin acetylation in distal segments of long peripheral nerves. Treatment with a new, highly selective HDAC6 inhibitor, SW-100, was able to restore α-tubulin acetylation and ameliorate motor and sensory dysfunction when given either prior to or after the onset of symptoms. To confirm HDAC6 is the target for ameliorating the CMT2A phenotype, we show that genetic deletion of Hdac6 in CMT2A mice prevents the development of motor and sensory dysfunction. Our findings suggest α-tubulin acetylation defects in distal parts of nerves as a pathogenic mechanism and HDAC6 as a therapeutic target for CMT2A.