MC1568

Names

[ Name ]:
MC1568

[Synonym ]:
MC1568
cc-402
(2E)-3-{4-[(1E)-3-(3-Fluorophenyl)-3-oxo-1-propen-1-yl]-1-methyl-1H-pyrrol-2-yl}-N-hydroxyacrylamide
S1484_Selleck
(2E)-3-{4-[(1E)-3-(3-fluorophenyl)-3-oxoprop-1-en-1-yl]-1-methyl-1H-pyrrol-2-yl}-N-hydroxyprop-2-enamide
(E)-3-(4-((E)-3-(3-fluorophenyl)-3-oxoprop-1-enyl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide
2-Propenamide, 3-[4-[(1E)-3-(3-fluorophenyl)-3-oxo-1-propen-1-yl]-1-methyl-1H-pyrrol-2-yl]-N-hydroxy-, (2E)-
MC-1568,MC1568

Biological Activity

[Description]:

MC1568 is a selective class II (IIa) histone deacetylas (HDAC II) inhibitor, used for cancer research.

[Related Catalog]:

Research Areas >> Cancer

[Target]

HDAC

[In Vitro]

MC1568 arrests myogenesis by decreasing myocyte enhancer factor 2D (MEF2D) expression, by stabilizing the HDAC4–HDAC3–MEF2D complex, and paradoxically, by inhibiting differentiation-induced MEF2D acetylation[1]. MC1568 and MC1575 inhibits IL-8 levels and cell proliferation in either unstimulated or PMA-stimulated melanoma cells. They acts by suppressing c-Jun binding to the IL-8 promoter, recruitment of histones 3 and 4, RNA polymerase II and TFIIB to the c-Jun promoter, and c-Jun expression[2]. MC1568 interferes with the RAR- and PPARγ-mediated differentiation-inducing signaling pathways. In F9 cells, this inhibitor specifically blocks endodermal differentiation. In 3T3-L1 cells, MC1568 attenuates PPARγ-induced adipogenesis[3].

[In Vivo]

MC1568 shows an apparent tissue-selective HDAC inhibition. In skeletal muscle and heart, MC1568 inhibits the activity of HDAC4 and HDAC5 without affecting HDAC3 activity, thereby leaving MEF2–HDAC complexes in a repressed state[1]. MC1568 increases mortality and lesion volume and did not improve functional outcome. In addition, MC1568 decreases microtubule associated protein 2, phosphorylated neurofilament heavy chain and myelin basic protein immunoreactivity in the periinfarct cortex[4].

[Cell Assay]

For proliferation studies, 15 ×103 cells are seeded onto 24-well plates in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 3 mM L-glutamine, 2% penicillin/streptomycin. After 24 h, untreated or HDACis-treated cells are incubated with either vehicle alone or PMA (50 ng/mL) for 6 h, and cell proliferation is evaluated by MTT assay and by cell number counting[2].

[Animal admin]

Adult male Wistar rats (n=15-17/group) are subjected to 2 h MCAO and orally gavaged with MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control for 7 days starting 24 h after MCAO. A battery of behavioral tests is performed. Lesion volume measurement and immunohistochemistry are performed 28 days after MCAO[4]

[References]

[1]. Nebbioso A, et al. Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity ofHDAC-MEF2 complexes. EMBO Rep. 2009 Jul;10(7):776-82.

[2]. Venza I, et al. Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment Cell Melanoma Res. 2013 Mar;26(2):193-204.

[3]. Nebbioso A, et al. HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation. J Mol Endocrinol. 2010 Oct;45(4):219-28.

[4]. Kassis H, et al. Class IIa histone deacetylases affect neuronal remodeling and functional outcome after stroke. Neurochem Int. 2016 Jun;96:24-31.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Molecular Formula ]:
C₁₇H₁₅FN₂O₃

[ Molecular Weight ]:
314.311

[ Exact Mass ]:
314.106659

[ PSA ]:
74.82000

[ LogP ]:
2.91

[ Appearance of Characters ]:
orange

[ Index of Refraction ]:
1.572

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: ≥10mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H319

[ Precautionary Statements ]:
P305 + P351 + P338

[ Hazard Codes ]:
Xn,Xi

[ Risk Phrases ]:
22-36

[ Safety Phrases ]:
26

[ RIDADR ]:
NONH for all modes of transport

Articles

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle.

FEBS Lett. 589(10) , 1080-8, (2015)

PKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this sign...

PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells.

PLoS ONE 10 , e0137699, (2015)

The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs) and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the express...

Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.

PLoS ONE 8(1) , e55786, (2013)

The conversion of a quiescent vitamin A storing hepatic stellate cell (HSC) to a matrix producing, contractile myofibroblast-like activated HSC is a key event in the onset of liver disease following i...