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化学情報
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Synonyms | Rocilinostat | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C24H27N5O3 |
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| 分子量 | 433.5 | CAS No. | 1316214-52-4 | |
| Solubility (25°C)* | 体外 | DMSO | 86 mg/mL (198.38 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Ricolinostat (ACY-1215, Rocilinostat) is a selective HDAC6 inhibitor with IC50 of 5 nM in a cell-free assay. It is >10-fold more selective for HDAC6 than HDAC1/2/3 (class I HDACs) with slight activity against HDAC8, minimal activity against HDAC4/5/7/9/11, Sirtuin1, and Sirtuin2. Ricolinostat (ACY-1215) suppresses cell proliferation and promotes apoptosis. Phase 2. |
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| in vitro | ACY-1215 is a hydroxamic acid derivative. ACY-1215 is 12-, 10-, and 11-fold less active against HDAC1, HDAC2, and HDAC3 (class I HDACs), respectively. ACY-1215 has minimal activity (IC50 > 1μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 = 0.1μM). The IC50 values for ACY-1215 for T-cell toxicity is 2.5μM. ACY-1215 overcomes tumor cell growth and survival conferred by BMSCs and cytokines in the BM milieu. ACY-1215 in combination with bortezomib induces synergistic anti-MM activity. ACY-1215 induces potent acetylation of α-tubulin at very low doses and triggers acetylation of lysine on histone H3 and histone H4 only at higher doses, confirming its specific inhibitory effect on HDAC6 activity. [1] |
| in vivo | ACY-1215 in combination with bortezomib triggered more significant anti-MM activity than either agent alone in suppressing tumor growth and prolonging survival in both plasmacytoma model and disseminated MM model without significant adverse effects. ACY-1215 is readily absorbed by tumor tissue. Moreover, the drug does not accumulate in tumor tissue, as evidenced by the parallel decline of acetylated α-tubulin in blood cells and tumor tissue by 24 hours after dose. [1] |
| 特徴 | Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA. |
プロトコル(参考用のみ)
| キナーゼアッセイ | HDAC enzymatic assays | |
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| ACY-1215 is dissolved and subsequently diluted in assay buffer [50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine] to 6-fold the final concentration. HDAC enzymes are diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with ACY-1215 for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction is calculated. | ||
| 細胞アッセイ | 細胞株 | MM cell lines, patient MM cells, and PBMCs |
| 濃度 | ~8 μM | |
| 反応時間 | 48 hours | |
| 実験の流れ | PBMCs from healthy donors are isolated and stimulated with 2.5 μg/mL of phytohemagglutinin (PHA) for 48 hours in the presence of increasing concentrations of ACY-1215. DNA synthesis is measured by tritiated thymidine uptake. CD4+T cells are purified from human blood with the Rosette Sep negative-selection kit. Cells are stimulated by CD3/CD28 Dynabeads for 7 days in the presence of compounds. Cell viability is assessed using alamarBlue. MM cells (2-3 × 104cells/well) are incubated in 96-well culture plates with medium and different concentrations of ACY-1215, bortezomib, and/or recombinant IL-6 (10 ng/mL) or insulin-like growth factor-1 (IGF-1; 50 ng/mL) for 24 hours at 37°C, and tritiated thymidine incorporation is measured. |
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| 動物実験 | 動物モデル | MM xenograft SCID mouse model |
| 投薬量 | 50 mg/kg | |
| 投与方法 | ip | |
カスタマーフィードバック
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, , Oncogene, 2017, 36(24):3450-3463
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, , Mol Cancer Ther, 2015, 14(3):727-39.
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Data from [Data independently produced by , , J Pathol, 2018, 246(2):141-153]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| HDAC6 inhibitor ACY-1215 enhances STAT1 acetylation to block PD-L1 for colorectal cancer immunotherapy [ Cancer Immunol Immunother, 2024, 73(1):7] | PubMed: 38231305 |
| HDAC Inhibition Induces CD26 Expression on Multiple Myeloma Cells via the c-Myc/Sp1-mediated Promoter Activation [ Cancer Res Commun, 2024, 4(2):349-364] | PubMed: 38284882 |
| Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC [ J Thorac Oncol, 2023, S1556-0864(23)00197-1] | PubMed: 36958689 |
| HDAC6 regulates human erythroid differentiation through modulation of JAK2 signalling [ J Cell Mol Med, 2023, 27(2):174-188] | PubMed: 36578217 |
| Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites [ Nat Cell Biol, 2022, 24(4):483-496] | PubMed: 35411088 |
| Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity [ Nat Metab, 2022, 4(1):44-59] | PubMed: 35039672 |
| Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor [ Cancers (Basel), 2022, 14(3)782] | PubMed: 35159049 |
| Ricolinostat enhances adavosertib‑induced mitotic catastrophe in TP53‑mutated head and neck squamous cell carcinoma cells [ Int J Oncol, 2022, 60(5)54] | PubMed: 35348191 |
| Ricolinostat suppresses proliferation, promotes apoptosis, and enhances the antiproliferative activity of topoisomerase inhibitors in cervical cancer cells [ Drug Dev Res, 2022, 10.1002/ddr.21999] | PubMed: 36173896 |
| PDI inhibitor LTI6426 enhances panobinostat efficacy in preclinical models of multiple myeloma [ Cancer Chemother Pharmacol, 2022, 89(5):643-653] | PubMed: 35381875 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。