1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERicolinostatCat. No.: HY-16026CAS No.: 1316214-52-4Synonyms: ACY-1215; Rocilinostat分式: CHNO分量: 433.5作靶點(diǎn): HDAC作通路: Cell Cycle/DNA Damage; Epigenetics儲(chǔ)存式: 4C, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (stor

2、ed undernitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (115.34 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3068 mL 11.5340 mL 23.0681 mL5 mM 0.4614 mL 2.3068 mL 4.6136 mL10 mM 0.2307 mL 1.1534 mL 2.3068 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)

3、動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.77 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.77 mM);

4、 Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.77 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Ricolinostat (ACY-1215)種有效，選擇性的 HDAC6 抑制劑，IC50 為 5 nM。ACY-1215 也可抑制HDAC1，HDAC2 和 HDAC3，IC50 分別為 58，48 和 51 nM。IC50 & Target HDAC6 H

5、DAC2 HDAC3 HDAC14.7 nM (IC50) 48 nM (IC50) 51 nM (IC50) 58 nM (IC50)HDAC8 HDAC7 HDAC5 HDAC4100 nM (IC50) 1400 nM (IC50) 5000 nM (IC50) 7000 nM (IC50)體外研究 Ricolinostat (ACY-1215) has slight activity against HDAC8 (IC50=0.1 M), and has minimal activity (IC501 M) against HDAC4, HDAC5, HDAC7, HDAC9, HDA

6、C11, Sirtuin1, and Sirtuin2. The effect of Ricolinostat(ACY-1215) on multiple myeloma (MM) cell viability is determined with MTT assays using MM cell lines.Exposure of MM cell lines for 48 hours results in dose-dependent decreased viability, with IC50 valuesranging from 2-8M. Ricolinostat (ACY-1215)

7、 demonstrates significant activity in the MM Bortezomib-resistant cell line (ANBL-6.BR), demonstrating the ability of Ricolinostat (ACY-1215) to overcome Bortezomibresistance 1.體內(nèi)研究 Mice treated with Ricolinostat (ACY-1215), Bortezomib, or Ricolinostat plus Bortezomib show a significantdelay in tumo

8、r growth (P=0.01, P=0.006, and P 1.PROTOCOLCell Assay 1 The effect of Ricolinostat with or without Bortezomib on the viability of MM cell lines, patient MM cells, andPBMCs is assessed by measuring MTT dye absorbance. PBMCs from healthy donors are isolated andstimulated with 2.5 g/mL of phytohemagglu

9、tinin (PHA) for 48 hours in the presence of increasingconcentrations of Ricolinostat (ACY-1215). DNA synthesis is measured by tritiated thymidine uptake. CD4+ Tcells are purified from human blood with the Rosette Sep negative-selection kit. Cells are stimulated byCD3/CD28 Dynabeads for 7 days in the

10、 presence of compounds. Cell viability is assessed using alamarBlue.MM cells (2-3104 cells/well) are incubated in 96-well culture plates with medium and differentconcentrations of Ricolinostat (ACY-1215), Bortezomib, and/or recombinant IL-6 (10 ng/mL) or insulin-likegrowth factor-1 (IGF-1; 50 ng/mL)

11、 for 24 hours at 37C, and tritiated thymidine incorporation is measured 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 To evaluate the in vivo anti-MM activity of Ricolinostat, male SCID mice are inoculated subcutaneousl

12、y with5106 MM.1S cells in 100 L of serum-free RPMI 1640 medium. When tumors are measurable, mice aretreated IP with Ricolinostat 50 mg/kg dissolved in 10% DMSO in 5% dextrose in water consecutively for 5days a week for 3 weeks; Bortezomib 0.5 mg/kg dissolved in 0.9% saline solution biweekly (IV) for

13、 32/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEconsecutive weeks; or combination with the same dosing regimen used for the individual agents. The controlgroup receive the carrier alone at the same schedule as the combination group. Tumor size is measuredevery other day in 2 dimensions using cali

14、pers, and tumor volume is calculated with the formula: V=0.5(ab2)where a is the long diameter of the tumor and b is the short diameter of the tumor. Mice are killed when thetumor reaches 2 cm3 or is ulcerated. Survival and tumor growth are evaluated from the first day of treatmentuntil death.MCE has

15、 not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Leukemia. 2019 Jul;33(7):1675-1686. Oncogene. 2018 Nov;37(45):5952-5966. Cancer Lett. 2016 Aug 28;379(1):134-142. J Mol Med (Berl). 2019 Jun 14. Biomed Pharmacother. 2019 Jan;109:2464-2471.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Santo L, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, incombination with bortezomib in multiple myeloma