ACY-738

Alias: ACY738; ACY 738; ACY-738

Cat No.:V2907 Purity: =98.98%

COA Product Data Instructions for use SDS

ACY-738 (ACY738) is a novel, potent, selective, brain penetrable and orally-bioavailable HDAC6 inhibitor with neuroprotective and anticancer activities.

ACY-738 Chemical Structure CAS No.: 1375465-91-0
Product category: HDAC

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: =98.98%

COA

MSDS

NMR

HPLC

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

ACY-738 (ACY738) is a novel, potent, selective, brain penetrable and orally-bioavailable HDAC6 inhibitor with neuroprotective and anticancer activities. It also inhibits HDAC1, HDAC2, and HDAC3, with IC50s of 94, 128, and 218 nM; its IC50 for HDAC6 is 1.7 nM. In RN46A-B14 cells, ACY-738 (2.5 μM) raises the acetylated (lysine 40) fraction of α-tubulin. Cell death induced by ACY-738 (10 μM) is similar to that of FK228 and LBH589. ACY-738 has a selectivity of 60–1500 times greater than class I HDACs and low nanomolar potency when inhibiting HDAC6. ACY-738 stimulates mouse exploratory behaviors in unfamiliar but novel environments and causes dramatic increases in α-tubulin acetylation in the brain, unlike tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity but less brain bioavailability.

Biological Activity I Assay Protocols (From Reference)

Targets

HDAC6 ( IC50 = 1.7 nM ); HDAC1 ( IC50 = 94 nM ); HDAC2 ( IC50 = 128 nM ); HDAC3 ( IC50 = 218 nM )

ln Vitro

ACY-738 (2.5 μM) raises the acetylated (lysine 40) fraction of α-tubulin in RN46A-B14 cells[1]. ACY-738 (10 μM) causes a similar amount of cell death as FK228 and LBH589[3].

ln Vivo

ACY-738 (5 mg/kg) significantly increases α-tubulin acetylation in whole-brain lysates. In WT mice examined in a home cage setting, ACY-738 (50 mg/kg) does not result in an increase in locomotor activity[1]. ACY-738 (5 mg/kg) takes 0.0830 hours to reach its maximum plasma concentration of 1310 ng/mL. IgG and C3 deposition in NZB/W mice are not significantly affected by ACY-738 (5 mg/kg BW), although it does change the differentiation of BM B cells. The severity of proteinuria in NZB/W F1 mice is significantly reduced by ACY-738 (20 mg/kg). With age, NZB/W mice treated with ACY-738 (5 mg/kg) produced significantly less anti-dsDNA. As the NZB/W mice aged, ACY-738 (5, 20 mg/kg) attenuated the production of IL-1β in the sera. While treatment with ACY-738 (20 mg/kg) reduced IL-6 and IL-10 mRNA to non-detectable levels, ACY-738 (5 mg/kg) significantly reduced glomerular IL-6 and IL-10 mRNA levels by more than 50%[2].

Enzyme Assay

ACY-738 is a newly developed HDAC6 inhibitor that is highly selective, potent, and orally bioavailable. Its IC50 is 1.7 nM, and it also inhibits HDAC1, HDAC2, and HDAC3 at IC50s of 94, 128, and 218 nM.

Cell Assay

In RN46A-B14 cells, ACY-738 (2.5 μM) raises the acetylated (lysine 40) fraction of α-tubulin.

Animal Protocol

5, 20, 50 mg/kg; i.p. and p.o.

In RN46A-B14 cells, ACY-738 (2.5 μM) raises the acetylated (lysine 40) fraction of α-tubulin.Beginning at 22 weeks of age and continuing until their euthanasia at 38 weeks, mice receive intraperitoneal injections five days a week of either the vehicle control (DMSO), ACY-738 treatment at 5 mg/kg (low-dose), or ACY-738 treatment at 20 mg/kg (high-dose). Eighty μL is the total volume injected. Every two weeks, weight and proteinuria are assessed, and every four weeks, blood is drawn for sera analysis. Siemens Uristix dipsticks are used in a standard semi-quantitative test to measure proteinuria. Dipstick readings of 0 mg/dL = 0, trace = 1, 30-100 mg/dL = 2, 100-300 mg/dL = 3, 300-2000 mg/dL = 4, and 2000 + mg/dL = 5 are the methods used to quantify and score the results[2].

References

[1]. Antidepressant-like properties of novel HDAC6-selective inhibitors with improved brain bioavailability. Neuropsychopharmacology. 2014 Jan;39(2):389-400.

[2]. Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice. Clin Immunol. 2016 Jan;162:58-73.

[3]. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol. 2013 Aug;162(4):559-62.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C14H14N4O2

Molecular Weight

270.29

Exact Mass

270.11

Elemental Analysis

C, 62.21; H, 5.22; N, 20.73; O, 11.84

CAS #

1375465-91-0

Related CAS #

1375465-91-0

Appearance

White to off-white solid powder

SMILES

C1CC1(C2=CC=CC=C2)NC3=NC=C(C=N3)C(=O)NO

InChi Key

LIIWIMDSZVNYHY-UHFFFAOYSA-N

InChi Code

InChI=1S/C14H14N4O2/c19-12(18-20)10-8-15-13(16-9-10)17-14(6-7-14)11-4-2-1-3-5-11/h1-5,8-9,20H,6-7H2,(H,18,19)(H,15,16,17)

Chemical Name

N-hydroxy-2-[(1-phenylcyclopropyl)amino]pyrimidine-5-carboxamide

Synonyms

ACY738; ACY 738; ACY-738

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 32 mg/mL

Water: <1 mg/mL

Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.08 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6997 mL	18.4986 mL	36.9973 mL
	5 mM	0.7399 mL	3.6997 mL	7.3995 mL
	10 mM	0.3700 mL	1.8499 mL	3.6997 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Concentration (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

ACY-738

Selectivity, potency, and pharmacokinetic properties of HDAC6 inhibitors used in this study. Top row (a–c): dose-dependent enzymatic inhibition of recombinant HDAC1, HDAC2, HDAC3, and HDAC6 incubated with (a) tubastatin A, (b) ACY-738, or (c) ACY-775. Middle row: (d) heat map summary of IC50 values for the novel inhibitors ACY-738 and ACY-775 and reference compounds SAHA, MS-275, and ACY-1215 (n=2 per condition).Neuropsychopharmacology.2014 Jan;39(2):389-400.

Effects of HDAC6 inhibitors onα-tubulin acetylation at lysine 40 (K40) and histone H3 acetylation at lysine 9 (H3K9)Neuropsychopharmacology.2014 Jan;39(2):389-400.
HDAC6 inhibitors ACY-738 and ACY-775 have antidepressant-like properties.
Effects of HDAC6-selective inhibition in anxiety tests.Neuropsychopharmacology.2014 Jan;39(2):389-400.