Ricolinostat (ACY-1215) is a potent and selective HDAC6 inhibitor, with an IC50 of 5 nM. ACY-1215 also inhibits HDAC1, HDAC2, and HDAC3 with IC50s of 58, 48, and 51 nM, respectively.
For research use only. We do not sell to patients.
The expression of IL-1β and IL-6 in human primary chondrocytes and C28/I2 cells is tested by western blot analysis with the treatment of IL-1β, DMSO and ACY-1215.
Mouse CAFs are treated with increasing concentrations of ACY1215 for 24 h. Western blot analysis of tubulin, histone H3, histone H4, acetylated tubulin, acetylated histone H3, and acetylated histone H4.
A375 cells are treated with indicated concentrations of ACY-1215. After 72 h, Western blotting assay are utilized to detect apoptosis.
Ricolinostat purchased from MedChemExpress. Usage Cited in:
Cancer Lett. 2016 Aug 28;379(1):134-142.
[Abstract]
Inhibition of HDAC6 by HDAC6-selective inhibitors impairs the proliferation of glioblastoma cells. U87 and U251 cells are treated with HDAC6 selective inhibitors and the cells are harvested for subsequent western blot analysis.
Ricolinostat purchased from MedChemExpress. Usage Cited in:
Med Oncol. 2016 May;33(5):50.
[Abstract]
H460 cells are treated with 0.5 μM Aorafenib and indicated concentration of HDAC6 inhibitors, CAY10603 (CAY, 0.05 μM) or ACY1215 (ACY,1 μM). The cleavage of PARP and caspase 3 also increased after cotreatment.
Ricolinostat (ACY-1215) is a potent and selective HDAC6 inhibitor, with an IC50 of 5 nM. ACY-1215 also inhibits HDAC1, HDAC2, and HDAC3 with IC50s of 58, 48, and 51 nM, respectively.
IC50 & Target
HDAC6
4.7 nM (IC50)
HDAC2
48 nM (IC50)
HDAC3
51 nM (IC50)
HDAC1
58 nM (IC50)
HDAC8
100 nM (IC50)
HDAC7
1400 nM (IC50)
HDAC5
5000 nM (IC50)
HDAC4
7000 nM (IC50)
In Vitro
Ricolinostat (ACY-1215) has slight activity against HDAC8 (IC50=0.1 μM), and has minimal activity (IC50>1 μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, 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 values ranging from 2-8μM. Ricolinostat (ACY-1215) demonstrates significant activity in the MM PS-341-resistant cell line (ANBL-6.BR), demonstrating the ability of Ricolinostat (ACY-1215) to overcome PS-341 resistance[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Ricolinostat Related Antibodies
In Vivo
Mice treated with Ricolinostat (ACY-1215), PS-341, or Ricolinostat plus PS-341 show a significant delay in tumor growth (P=0.01, P=0.006, and P<0.0001, respectively). Combined treatment with Ricolinostat and PS-341 shows significant suppression of tumor growth and significantly prolonged overall survival (OS) compare with the control group (17 days in the control vs 40 days in the combination-treated group, P<0.0001) and the Ricolinostat (ACY-1215)-treated group (22 days in the PS-341 group vs 40 days in the combination-treated group, P<0.0001). Weight loss in the combination-treated group is between 4% and 12% compare with the same-day control group values during treatment, with complete recovery after the last injection. As is observed in the plasmacytoma model, a significant therapeutic advantage is found by combining Ricolinostat with PS-341 compare with either agent alone[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
DMSO : ≥ 50 mg/mL (115.34 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.3068 mL
11.5340 mL
23.0681 mL
5 mM
0.4614 mL
2.3068 mL
4.6136 mL
10 mM
0.2307 mL
1.1534 mL
2.3068 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (stored under nitrogen). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.77 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Santo L, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with PS-341 in multiple myeloma. Blood. 2012 Mar 15;119(11):2579-89.
[Content Brief]
Cell Assay
[1]
The effect of Ricolinostat with or without PS-341 on the viability of MM cell lines, patient MM cells, and PBMCs is assessed by measuring MTT dye absorbance. 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 Ricolinostat (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 (2-3×104 cells/well) are incubated in 96-well culture plates with medium and different concentrations of Ricolinostat (ACY-1215), PS-341, and/or recombinant IL-6 (10 ng/mL) or IGF-1 (50 ng/mL) for 24 hours at 37°C, and tritiated thymidine incorporation is measured[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]
Mice[1] To evaluate the in vivo anti-MM activity of Ricolinostat, male SCID mice are inoculated subcutaneously with 5×106 MM.1S cells in 100 μL of serum-free RPMI 1640 medium. When tumors are measurable, mice are treated IP with Ricolinostat 50 mg/kg dissolved in 10% DMSO in 5% dextrose in water consecutively for 5 days a week for 3 weeks; PS-341 0.5 mg/kg dissolved in 0.9% saline solution biweekly (IV) for 3 consecutive weeks; or combination with the same dosing regimen used for the individual agents. The control group receive the carrier alone at the same schedule as the combination group. Tumor size is measured every other day in 2 dimensions using calipers, and tumor volume is calculated with the formula: V=0.5(a×b2) where a is the long diameter of the tumor and b is the short diameter of the tumor. Mice are killed when the tumor reaches 2 cm3 or is ulcerated. Survival and tumor growth are evaluated from the first day of treatment until death.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References
[1]. Santo L, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with PS-341 in multiple myeloma. Blood. 2012 Mar 15;119(11):2579-89.
[Content Brief]
[1]. Santo L, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with PS-341 in multiple myeloma. Blood. 2012 Mar 15;119(11):2579-89.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (stored under nitrogen). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.3068 mL
11.5340 mL
23.0681 mL
57.6701 mL
5 mM
0.4614 mL
2.3068 mL
4.6136 mL
11.5340 mL
10 mM
0.2307 mL
1.1534 mL
2.3068 mL
5.7670 mL
15 mM
0.1538 mL
0.7689 mL
1.5379 mL
3.8447 mL
20 mM
0.1153 mL
0.5767 mL
1.1534 mL
2.8835 mL
25 mM
0.0923 mL
0.4614 mL
0.9227 mL
2.3068 mL
30 mM
0.0769 mL
0.3845 mL
0.7689 mL
1.9223 mL
40 mM
0.0577 mL
0.2884 mL
0.5767 mL
1.4418 mL
50 mM
0.0461 mL
0.2307 mL
0.4614 mL
1.1534 mL
60 mM
0.0384 mL
0.1922 mL
0.3845 mL
0.9612 mL
80 mM
0.0288 mL
0.1442 mL
0.2884 mL
0.7209 mL
100 mM
0.0231 mL
0.1153 mL
0.2307 mL
0.5767 mL
Ricolinostat Related Classifications
Cell Cycle/DNA DamageEpigeneticsApoptosis
HDACApoptosis
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.