Rocilinostat (ACY-1215)

Catalog No.S8001

Rocilinostat (ACY-1215) is a selective HDAC6 inhibitor with IC50 of 5 nM. 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. Phase 2.

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In DMSO USD 190 In stock
USD 110 In stock
USD 170 In stock
USD 570 In stock
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Rocilinostat (ACY-1215) Chemical Structure

Rocilinostat (ACY-1215) Chemical Structure
Molecular Weight: 433.5

Validation & Quality Control

Quality Control & MSDS

HDAC Inhibitors with Unique Features

Product Information

  • Inhibition Profile
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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Rocilinostat (ACY-1215) is a selective HDAC6 inhibitor with IC50 of 5 nM. 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. Phase 2.
Targets HDAC6 [1] HDAC2 [1] HDAC3 [1] HDAC1 [1] HDAC8 [1]

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IC50 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. 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]
Features Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA.

Protocol(Only for 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.

Animal Study: [1]

Animal Models MM xenograft SCID mouse model
Formulation 10% DMSO in 5% dextrose in water
Dosages 50 mg/kg
Administration ip
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80, , 30 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Santo L, et al. Blood, 2012, 119(11), 2579-2589.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-09-01)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02189343 Not yet recruiting Multiple Myeloma Acetylon Pharmaceuticals Incorporated July 2014 Phase 1
NCT02091063 Recruiting Lymphoma|Lymphoid Malignancies Columbia University|Jennifer Amengual|Acetylon Pharmaceuticals Incorporated March 2014 Phase 1|Phase 2
NCT02088398 Recruiting Healthy Acetylon Pharmaceuticals Incorporated March 2014 Phase 1
NCT01997840 Recruiting Multiple Myeloma Acetylon Pharmaceuticals Incorporated November 2013 Phase 1|Phase 2
NCT01583283 Recruiting Multiple Myeloma Acetylon Pharmaceuticals Incorporated April 2012 Phase 1|Phase 2

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Chemical Information

Download Rocilinostat (ACY-1215) SDF
Molecular Weight (MW) 433.5
Formula

C24H27N5O3

CAS No. 1316214-52-4
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 87 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL
* <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.
Chemical Name 5-Pyrimidinecarboxamide, 2-(diphenylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-

Research Area

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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