MC1568

Alias: MC1568; MC 1568; MC-1568
Cat No.:V0288 Purity: ≥98%
MC1568isa hydroxyamide-based inhibitor of class II histone deacetylase (HDAC) such as HDAC4/5/6/7/9 (IIa) and HDAC6/10 (IIb) with potential antiviral activity.
MC1568 Chemical Structure CAS No.: 852475-26-4
Product category: HDAC
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

MC1568 is a hydroxyamide-based inhibitor of class II histone deacetylase (HDAC) such as HDAC4/5/6/7/9 (IIa) and HDAC6/10 (IIb) with potential antiviral activity. It blocks the influenza A virus from multiplying.

Biological Activity I Assay Protocols (From Reference)
Targets
HD1-A ( IC50 = 100 nM ); HD1-B ( IC50 = 3.4 μM )
ln Vitro

In vitro activity: MC1568 is a 176-fold class II selectivity (against class I) selective class II (IIa) histone deacetylase inhibitor with an IC50 of 220 nM. MC1568 (5 μM) does not exhibit any inhibitory activity against HDAC1 in human breast cancer ZR-75.1 cell lysates, but it can inhibit HDAC4.[1] MC1568 (20 μM) increases the levels of acetyl-tubulin and the accumulation of acetylated H3 and H4 histones in MCF-7 cells, suggesting that MC1568 inhibits HDAC6.[2] MC1568 (5 μM) stops myogenesis in C2C12 cells by blocking differentiation-induced MEF2D acetylation, stabilizing the HDAC4-HDAC3-MEF2D complex, and reducing the expression of myocyte enhancer factor 2D (MEF2D).[3] MC1568 (5 or 10 μM) disrupts the signaling pathways that induce differentiation mediated by RAR and PPARγ. MC1568 does not alter the maturation of promyelocytic NB4 cells induced by retinoic acid, but it specifically inhibits endodermal differentiation in F9 cells. MC1568 reduces PPARγ-induced adipogenesis in 3T3-L1 cells.[4]

ln Vivo
MC1568 (50 mg/kg) in mice appears to inhibit HDAC in a tissue-selective manner. MEF2-HDAC complexes in skeletal muscle and the heart are in a repressed state because MC1568 suppresses HDAC4 and HDAC5 activity while leaving HDAC3 activity unaffected.[3] MC1568 (50 mg/kg) primarily affects PPARγ signaling in the heart and adipose tissues in PPRE-Luc mice.[4] According to a recent study on pancreatic explants, MC1568 increases the expression of Pax4, which is essential for the correct differentiation of β- and δ-cells and increases the number of endocrine β- and δ-cells.[5]
Enzyme Assay
Scintillation counting is used to measure the amount of tritiated acetic acid that the enzyme extracts from the substrate. Triple determinations produce IC50 values. Ten microliters of total [3H]acetate-prelabeled chicken reticulocyte histones (2 mg/mL) are incubated for 30 minutes with a 50 μL sample of maize enzyme at 30 °C. To halt the reaction, add 800 μL of ethyl acetate and 50 μL of 1 M HCl/0.4 M acetate. A 600 μL aliquot of the upper phase is centrifuged at 1×104 g for 5 minutes, and its radioactivity is measured in 3 mL of liquid scintillation cocktail. Active ingredients are further diluted after MC1568 is tested at a starting concentration of 40 μM. The reference compounds are NaB, VPA, TSA, SAHA, 85 TPX, HC-toxin, and tubacin; the negative controls are blank solvents.
Cell Assay
Using a combination of insulin, dexamethasone, and isobutylmethylxanthine, 3T3-L1 cells are grown and differentiated. During the eight-day differentiation period starting on the second day after confluence, the 3T3-L1 cells are stimulated by: (1) No induction: the cells are cultured with DMSO or MC1568 at post-confluence and for the entire 8-day differentiation period. (2) Troglitazone: the cells are induced with 5 μM troglitazone, MC1568, or both at post-confluence and for the duration of the 8-day differentiation period. (3) Rosiglitazone: the cells are cultured with 1 μM rosiglitazone and either DMSO or MC1568 at post-confluence and for the duration of the 8-day differentiation period. (4) Dexamethasone and rosiglitazone: the cells were given 390 ng/mL dexamethasone and 1 μM rosiglitazone at post-confluence. The cells are induced with 1 μM rosiglitazone and either DMSO or MC1568 for the duration of the 8-day differentiation period. Every two days, all media are refreshed.
Animal Protocol
Male Wistar adult rats (n=15–17/group) are given a 2-hour MCAO and then, starting 24 hours after MCAO, are given either MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control oral gavage for seven days. A series of behavioral assessments are conducted. 28 days following MCAO, lesion volume measurement and immunohistochemistry are carried out.
References

[1]. J Med Chem . 2005 May 5;48(9):3344-53.

[2]. Mol Cancer Res . 2008 Dec;6(12):1908-19.

[3]. EMBO Rep . 2009 Jul;10(7):776-82.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H15FN2O3
Molecular Weight
314.31
Exact Mass
314.11
Elemental Analysis
C, 64.96; H, 4.81; F, 6.04; N, 8.91; O, 15.27
CAS #
852475-26-4
Related CAS #
852475-26-4
Appearance
Solid powder
SMILES
CN1C=C(C=C1/C=C/C(=O)NO)/C=C/C(=O)C2=CC(=CC=C2)F
InChi Key
QRDAPCMJAOQZSU-KQQUZDAGSA-N
InChi Code
InChI=1S/C17H15FN2O3/c1-20-11-12(9-15(20)6-8-17(22)19-23)5-7-16(21)13-3-2-4-14(18)10-13/h2-11,23H,1H3,(H,19,22)/b7-5+,8-6+
Chemical Name
(E)-3-[4-[(E)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-N-hydroxyprop-2-enamide
Synonyms
MC1568; MC 1568; MC-1568
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: ~13 mg/mL (~41.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: 1 mg/mL (3.18 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: 0.5% CMC: 5mg/mL

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Solubility in Formulation 3: 2.5 mg/mL (7.95 mM) in 17% Polyethylene glycol 12-hydroxystearate in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.1816 mL 15.9079 mL 31.8157 mL
5 mM 0.6363 mL 3.1816 mL 6.3631 mL
10 mM 0.3182 mL 1.5908 mL 3.1816 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.

(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
  • MC1568 stabilize the MEF2–HDAC4–HDAC3 complex and blocks myogenesis of C2C12 cells. EMBO Rep . 2009 Jul;10(7):776-82.
  • MC1568 blocks MEF2D transcriptional activity in C2C12 cells and shows inhibitory activities in mice. EMBO Rep . 2009 Jul;10(7):776-82.
  • Effects of MC1575 and MC1568 on deacetylase activity in MCF-7 cells. Mol Cancer Res . 2008 Dec;6(12):1908-19.
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