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                同义名:
                    
                        
                            N-羟基-N'-苯基辛二酰胺
                            
                             / SAHA; Suberoylanilide hydroxamic acid
                            
                        
                    
                
                
                
                    
                     
                    
                     
                
            
Vorinostat (SAHA) 是一种高效、口服活性的 HDAC1、HDAC2、HDAC3 (I 类)、HDAC6、HDAC7 (II 类) 和 HDAC11 (IV 类) 的泛抑制剂,对 HDAC1 和 HDAC3 的 ID50 分别为 10 nM 和 20 nM。伏立诺他诱导细胞凋亡并抑制 HPV-18 DNA 扩增。
 
                                 
                                
                            

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| 产品名称 | HD1 ↓ ↑ | HD2 ↓ ↑ | HDAC ↓ ↑ | HDAC1 ↓ ↑ | HDAC10 ↓ ↑ | HDAC11 ↓ ↑ | HDAC2 ↓ ↑ | HDAC3 ↓ ↑ | HDAC4 ↓ ↑ | HDAC5 ↓ ↑ | HDAC6 ↓ ↑ | HDAC7 ↓ ↑ | HDAC8 ↓ ↑ | HDAC9 ↓ ↑ | 其他靶点 | 纯度 | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Givinostat HCl monohydrate | ++++ HD1-A, IC50: 16 nM HD1-B, IC50: 7.5 nM | +++ HD2, IC50: 10 nM | 99%+ | ||||||||||||||||
| MC1568 | ++ HD1-B (Maize), IC50: 3.4 μM HD1-A (Maize), IC50: 100 nM | 96% | |||||||||||||||||
| Trichostatin A | ++++ HDAC, IC50: ~1.8 nM | 99%+ | |||||||||||||||||
| Scriptaid | ✔ | 99%+ | |||||||||||||||||
| Valproic acid sodium | ✔ | Autophagy | 97% | ||||||||||||||||
| AR-42 | +++ HDAC, IC50: 30 nM | 99%+ | |||||||||||||||||
| Dacinostat | +++ HDAC, IC50: 32 nM | 98+% | |||||||||||||||||
| CUDC-101 | ++++ HDAC, IC50: 4.4 nM | ++++ HDAC1, IC50: 4.5 nM | +++ HDAC10, IC50: 26.1 nM | +++ HDAC2, IC50: 12.6 nM | ++++ HDAC3, IC50: 9.1 nM | +++ HDAC4, IC50: 13.2 nM | +++ HDAC5, IC50: 11.4 nM | ++++ HDAC6, IC50: 5.1 nM | + HDAC7, IC50: 373 nM | ++ HDAC8, IC50: 79.8 nM | ++ HDAC9, IC50: 67.2 nM | EGFR,HER2 | 99%+ | ||||||
| M344 | ++ HDAC, IC50: 100 nM | 99%+ | |||||||||||||||||
| Splitomicin | + Sir2p, IC50: 60 μM | 99% | |||||||||||||||||
| Panobinostat | ++++ HDAC (Reh cells), IC50: 20 nM HDAC (MOLT-4 cells), IC50: 5 nM | 98% | |||||||||||||||||
| Sodium 4-Phenylbutyrate | ✔ | 98% | |||||||||||||||||
| Vorinostat | +++ HDAC, IC50: ~10 nM | 98% | |||||||||||||||||
| Curcumin | ✔ | NF-κB,Nrf2 | 98% | ||||||||||||||||
| Belinostat | +++ HDAC, IC50: 27 nM | 98% | |||||||||||||||||
| RG-2833 | ++ HDAC1, Ki: 32 nM | ++ HDAC3, Ki: 5 nM | 98% | ||||||||||||||||
| Valproic acid | + HDAC1, IC50: 0.4 mM | 98% | |||||||||||||||||
| BG45 | + HDAC1, IC50: 2 μM | + HDAC2, IC50: 2.2 μM | + HDAC3, IC50: 289 nM | 99%+ | |||||||||||||||
| Entinostat | + HDAC1, IC50: 0.51 μM | + HDAC3, IC50: 1.7 μM | 98% | ||||||||||||||||
| Resminostat | +++ HDAC1, IC50: 42.5 nM | ++ HDAC3, IC50: 50.1 nM | ++ HDAC6, IC50: 71.8 nM | 98+% | |||||||||||||||
| Romidepsin | +++ HDAC1, IC50: 36 nM | +++ HDAC2, IC50: 47 nM | 99%+ | ||||||||||||||||
| Parthenolide | ✔ | NF-κB,p53 | 97% HPLC | ||||||||||||||||
| Tacedinaline | + HDAC1, IC50: 0.9 μM | + HDAC2, IC50: 0.9 μM | + HDAC3, IC50: 1.2 μM | 98% | |||||||||||||||
| Mocetinostat | ++ HDAC1, IC50: 0.15 μM | + HDAC11, IC50: 0.59 μM | + HDAC2, IC50: 0.29 μM | + HDAC3, IC50: 1.66 μM | 98% | ||||||||||||||
| WT-161 | ++++ HDAC1, IC50: 8.35 nM | +++ HDAC2, IC50: 15.4 nM | ++++ HDAC6, IC50: 0.4 nM | 99%+ | |||||||||||||||
| Fimepinostat | ++++ HDAC1, IC50: 1.7 nM | ++++ HDAC10, IC50: 2.8 nM | ++++ HDAC11, IC50: 5.4 nM | ++++ HDAC2, IC50: 5.0 nM | ++++ HDAC3, IC50: 1.8 nM | +++ HDAC6, IC50: 27 nM | 99%+ | ||||||||||||
| Tucidinostat | ++ HDAC1, IC50: 95 nM | ++ HDAC10, IC50: 78 nM | ++ HDAC2, IC50: 160 nM | ++ HDAC3, IC50: 67 nM | 99%+ | ||||||||||||||
| Santacruzamate A | ++++ HDAC2, IC50: 119 pM | 99%+ | |||||||||||||||||
| (E,E)-RGFP966 | ++ HDAC3, IC50: 80 nM | 99%+ | |||||||||||||||||
| LMK-235 | +++ HDAC4, IC50: 11.9 nM | ++++ HDAC5, IC50: 4.2 nM | 99%+ | ||||||||||||||||
| Tasquinimod | ✔ | 99%+ | |||||||||||||||||
| CAY10603 | ++++ HDAC6, IC50: 2 pM | 98% | |||||||||||||||||
| Tubastatin A | +++ HDAC6, IC50: 15 nM | 98% | |||||||||||||||||
| Tubacin | ++++ HDAC6, IC50: 4 nM | 99%+ | |||||||||||||||||
| ACY-738 | ++++ HDAC6, IC50: 1.7 nM | 99%+ | |||||||||||||||||
| Nexturastat A | ++++ HDAC6, IC50: 5 nM | 99%+ | |||||||||||||||||
| BRD73954 | +++ HDAC6, IC50: 36 nM | ++ HDAC8, IC50: 120 nM | 99% | ||||||||||||||||
| Tubastatin A HCl | +++ HDAC6, IC50: 15 nM | + HDAC8, IC50: 854 nM | 98% | ||||||||||||||||
| PCI-34051 | +++ HDAC8, IC50: 10 nM | 99%+ | |||||||||||||||||
| Ricolinostat | ++ HDAC1, IC50: 58 nM | ++ HDAC2, IC50: 48 nM | ++ HDAC3, IC50: 51 nM | ++++ HDAC6, IC50: 4.7 nM | ++ HDAC8, IC50: 100 nM | 99%+ | |||||||||||||
| Droxinostat | + HDAC3, IC50: 16.9 μM | + HDAC6, IC50: 2.47 μM | + HDAC8, IC50: 1.46 μM | 99%+ | |||||||||||||||
| Abexinostat | ++++ HDAC1, Ki: 7 nM | +++ HDAC10, IC50: 24 nM | +++ HDAC2, Ki: 19 nM | ++++ HDAC3/SMRT, Ki: 8.2 nM | +++ HDAC6, Ki: 17 nM | + HDAC8, IC50: 280 nM | 98%+ | ||||||||||||
| Citarinostat | +++ HDAC1, IC50: 35 nM | +++ HDAC2, IC50: 45 nM | +++ HDAC3, IC50: 46 nM | ++++ HDAC6, IC50: 2.6 nM | ++ HDAC8, IC50: 137 nM | 99%+ | |||||||||||||
| HPOB | + HDAC1, IC50: 2.9 μM | + HDAC10, IC50: 3.0 μM | + HDAC2, IC50: 4.4 μM | + HDAC3, IC50: 1.7 μM | ++ HDAC6, IC50: 56 nM | + HDAC8, IC50: 2.8 μM | 97% | ||||||||||||
| Quisinostat 2HCl | ++++ HDAC1, IC50: 0.11 nM | ++++ HDAC10, IC50: 0.46 nM | ++++ HDAC11, IC50: 0.37 nM | ++++ HDAC2, IC50: 0.33 nM | ++++ HDAC3, IC50: 4.86 nM | ++++ HDAC4, IC50: 0.64 nM | ++++ HDAC5, IC50: 3.69 nM | ++++ HDAC8, IC50: 4.26 nM | 97% | ||||||||||
| Domatinostat | + HDAC1, IC50: 1.20 μM | + HDAC10, IC50: 21 μM | + HDAC11, IC50: 9.7 μM | + HDAC2, IC50: 1.12 μM | + HDAC3, IC50: 0.57 μM | + HDAC5, IC50: 11.3 μM | + HDAC9, IC50: 50 μM | 99%+ | |||||||||||
| TMP269 | ++ HDAC4, IC50: 157 nM | ++ HDAC5, IC50: 97 nM | +++ HDAC7, IC50: 43 nM | +++ HDAC9, IC50: 23 nM | 99%+ | ||||||||||||||
| Pracinostat | ++ HDAC1, IC50: 49 nM | +++ HDAC10, IC50: 40 nM | ++ HDAC11, IC50: 93 nM | ++ HDAC2, IC50: 96 nM | +++ HDAC3, IC50: 43 nM | ++ HDAC4, IC50: 56 nM | +++ HDAC5, IC50: 47 nM | + HDAC6, IC50: 1.008 μM | ++ HDAC7, IC50: 137 nM | ++ HDAC8, IC50: 140 nM | ++ HDAC9, IC50: 70 nM | 99%+ | |||||||
| TMP195 | ++ HDAC4, Ki: 59 nM | ++ HDAC5, Ki: 60 nM | +++ HDAC7, Ki: 26 nM | +++ HDAC9, Ki: 15 nM | 99%+ | ||||||||||||||
| 1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。 | |||||||||||||||||||
| 产品名称 | Autophagy ↓ ↑ | 其他靶点 | 纯度 | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SBI-0206965 | +++ ULK2, IC50: 711 nM ULK1, IC50: 108 nM | 95% | |||||||||||||||||
| Hydroxychloroquine sulfate | ✔ | 99% | |||||||||||||||||
| Valproic acid sodium | ✔ | HDAC | 97% | ||||||||||||||||
| PFK-015 | ++ PFKFB3, IC50: 207 nM | 99%+ | |||||||||||||||||
| MRT68921 HCl | ++++ ULK2, IC50: 1.1 nM ULK1, IC50: 2.9 nM | 99%+ | |||||||||||||||||
| ROC-325 | ✔ | 99%+ | |||||||||||||||||
| Autophinib | +++ Autophagy, IC50: 40 nM | 99% | |||||||||||||||||
| Lys05 | ✔ | 99%+ | |||||||||||||||||
| 1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。 | |||||||||||||||||||
| 靶点 | 
 | 
| 描述 | HDACs (Histone deacetylases) are a group of enzymes that remove acetyl groups and regulate the histone tail, protein-DNA interaction, chromatin conformation, and even transcription. There are 18 mammalian HDACs divided into four classes: class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (sirtuin family: sirt1-sirt7) and class IV (HDAC 11)[1]. Vorinostat, also called as SAHA or MK0683, is a hydroxamic acid based class I and II HDACs pan inhibitor with IC50 value of 10nM on HDAC1 and 20 nM on HDAC3 (measured by immunoprecipitation–HDAC assays)[2]. Treatement with 6 μM of vorinostat in SH-SY5Y cells for 1 - 12 hours can increase the acetylation signals of histone H3 and H4 in a time-dependent manner. Vorinostat can induce cell-growth inhibition in SH-SY5Y cell line with IC50 value of 2.5 μM and 10 μM at 72h and 48h, respectively. SILAC-based quantitative MS analysis show that SAHA has a dramatic impact on histone lysine acetylation and butyrylation with strong increase in H3K9ac, H3K27ac, H2BK5bu and H4K12bu of SHSY5Y cells. Vorinostat is clinically approved for cutaneous T-cell lymphoma[3]. Both of gene expression and function of proteins regulating cell proliferation and cell death pathways are involved in the anticancer effects of SAHA, including TFIIB, Rb, Hsp90, Bcl-2 family, tubulin, HIF-1a, ROS, etc.[4]. | 
| 作用机制 | Vorinostat, structurally similar to TSA, chelates the zinc ion of HDACs by its hydroxamic group[5]. | 
| Concentration | Treated Time | Description | References | |
| Breast cancer cells (MDA-MB-231) | 1 µM and 3 µM | 5 h daily for 4 consecutive days | Vorinostat significantly decreased HDAC activity and inhibited cellular proliferation in a dose-dependent manner, with no significant effect on cell viability. | Oncotarget. 2016 Feb 16;7(7):7390-402. | 
| Prostate cancer cells (LNCaP) | 1 µM and 3 µM | 5 h daily for 4 consecutive days | Vorinostat significantly decreased HDAC activity and inhibited cellular proliferation in a dose-dependent manner, with no significant effect on cell viability. | Oncotarget. 2016 Feb 16;7(7):7390-402. | 
| HCT-8 cells | 203 nM | 44 h | To evaluate the inhibitory effect of Vorinostat on the growth of Cryptosporidium parvum, the results showed that Vorinostat significantly inhibited parasite growth in vitro. | J Infect Dis. 2018 Mar 13;217(7):1110-1117. | 
| Administration | Dosage | Frequency | Description | References | ||
| Nude mice | DU145 xenograft model | SAHA intraperitoneal injection, veliparib oral gavage | 25 mg/kg/d | 3 continuous weeks | To validate the antitumor effect of SAHA and veliparib co-treatment. Results showed that co-treatment significantly inhibited tumor growth. | J Exp Clin Cancer Res. 2018 Jul 16;37(1):153. | 
| Mice | IL-12 knockout mouse model | Oral | 7.5 mg/kg | Once daily for 6 days | To evaluate the inhibitory effect of Vorinostat on Cryptosporidium parvum infection in vivo, the results showed that Vorinostat significantly reduced the production of parasite oocysts. | J Infect Dis. 2018 Mar 13;217(7):1110-1117. | 
| Nude mice | HuCC-T1 tumor model | Subcutaneous injection | 10 mg/kg | Vorinostat nanofibers showed higher inhibition of tumor growth in HuCC-T1 tumor-bearing mice. | Int J Nanomedicine. 2017 Oct 17;12:7669-7680 | 
| Dose | Mice (i.p.): min = 50 mg/kg[6], max = 200 mg/kg[7] | ||||||||||||||||
| Administration | i.p. | ||||||||||||||||
| Pharmacokinetics | 
 | 
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 | 
| NCT00771472 | Lymphoma | Phase 1 | Completed | - | - | 
| NCT00771472 | - | Completed | - | - | |
| NCT01064921 | Stage III Squamous Cell Carcin... 展开 >>oma of the Oropharynx Stage IV Squamous Cell Carcinoma of the Oropharynx 收起 << | Phase 1 | Completed | - | United States, Ohio ... 展开 >> The Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210 收起 << | 
| 计算器 | ||||
| 存储液制备 |  | 1mg | 5mg | 10mg | 
| 1 mM 5 mM 10 mM | 3.78mL 0.76mL 0.38mL | 18.92mL 3.78mL 1.89mL | 37.83mL 7.57mL 3.78mL | |
| CAS号 | 149647-78-9 | 
| 分子式 | C14H20N2O3 | 
| 分子量 | 264.32 | 
| SMILES Code | O=C(NO)CCCCCCC(NC1=CC=CC=C1)=O | 
| MDL No. | MFCD00945317 | 
| 别名 | N-羟基-N'-苯基辛二酰胺 ;SAHA; Suberoylanilide hydroxamic acid; MK-0683, MK 0683, MK0683, SAHA, M344, CCRIS 8456, HSDB 7930, Vorinostat, suberoylanilide hydroxamic acid, Zolinza; MK0683 | 
| 运输 | 蓝冰 | 
| InChI Key | WAEXFXRVDQXREF-UHFFFAOYSA-N | 
| Pubchem ID | 5311 | 
| 存储条件 | In solvent -20°C: 3-6个月 -80°C: 12个月 Pure form Keep in dark place, inert atmosphere, store in freezer, under -20°C | 
| 溶解方案 | DMSO: 105 mg/mL(397.25 mM),注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO 以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 
 
 
 
 
 
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