Ricolinostat (ACY-1215)

Catalog No.S8001 Batch:S800103

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Technical Data

Formula

C24H27N5O3
Molecular Weight 433.5 CAS No. 1316214-52-4
Solubility (25°C)* In vitro DMSO 86 mg/mL (198.38 mM)
Water Insoluble
Ethanol Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
HDAC6 [1]
(Cell-free assay)		 HDAC2 [1]
(Cell-free assay)		 HDAC3 [1]
(Cell-free assay)		 HDAC1 [1]
(Cell-free assay)		 HDAC8 [1]
(Cell-free assay)
4.7 nM 48 nM 51 nM 58 nM 100 nM
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.
In vivo

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]
Features Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA.

Protocol (from reference)

Kinase Assay:

[1]
  • HDAC enzymatic assays

    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.

Cell Assay:

[1]
  • Cell lines

    MM cell lines, patient MM cells, and PBMCs

  • Concentrations

    ~8 μM

  • Incubation Time

    48 hours

  • Method

    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. 
Animal Study:

[1]
  • Animal Models

    MM xenograft SCID mouse model

  • Dosages

    50 mg/kg

  • Administration

    ip

Customer Product Validation

, , Oncogene, 2017, 36(24):3450-3463

, , Mol Cancer Ther, 2015, 14(3):727-39.

Data from [Data independently produced by , , J Pathol, 2018, 246(2):141-153]

Data from [Data independently produced by , , Br J Cancer, 2018, 119(10):1278-1287]

Selleck's Ricolinostat (ACY-1215) has been cited by 70 publications

HDAC6 inhibitor ACY-1215 enhances STAT1 acetylation to block PD-L1 for colorectal cancer immunotherapy [ Cancer Immunol Immunother, 2024, 73(1):7] PubMed: 38231305
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
The lysosomal Ragulator complex activates NLRP3 inflammasome in vivo via HDAC6 [ EMBO J, 2023, 42(1):e111389] PubMed: 36444797
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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