Mocetinostat (MGCD0103)

製品コードS1122 バッチS112205

化学情報

	Synonyms	MG0103	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₃H₂₀N₆O
	分子量	396.44	CAS No.	726169-73-9
Solubility (25°C)*	体外	DMSO	79 mg/mL (199.27 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Mocetinostat (MGCD0103, MG0103) is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8. Mocetinostat (MGCD0103) induces apoptosis and autophagy. Phase 2.
in vitro	MGCD0103 inhibits only a subset of the nine human recombinant HDACs, including HDAC1, HDAC2, HDAC3, and HDAC11 at nanomolar or low micromolar concentrations, in a dose-dependent manner. MGCD0103 reveals most potent inhibitory activity against human HDAC1 and HDAC2 enzymes in vitro, and it does not inhibit class II HDACs. The exocyclic amino group in MGCD0103 is necessary for enzyme inhibitory activity because HDAC-inhibitory activity against HDAC1 and HDAC2 is completely abolished with the desamino analogue. The inhibitory activity of MGCD0103 reaches the maximum plateau at 6 μM, and the maximal inhibitable enzyme pool affected by MGCD0103 is 75% of the total enzyme activity in HCT116 cells whereas NVP-LAQ824 inhibits almost 100% of that in these cells. In A549 cells, MGCD0103 also exhibits dose-dependent inhibition of HDAC activity in whole cells. ^[1]
in vivo	MGCD0103 significantly inhibites growth of human tumor xenografts in nude mice and the antitumor activity correlated with induction of histone acetylation in tumors. P.O. administration of MGCD0103 (2HBr salt) significantly decreases growth of implanted advanced A549 tumors in nude mice in a dose-dependent manner after 13 days of daily administration. MGCD0103 (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blockes growth of tumors compared with vehicle treatment alone with no change in body weight. In addition, MGCD0103 does not reduce WBC counts and is well tolerated. MGCD0103 is also orally active in many other human tumor xenograft models including NSCLC H1437. MGCD0103 at 80 mg/kg (free base) almost completely blocks the growth of H1437 tumors after 13 days of daily p.o. administration with no reduction of body weight in animals. ^[1] MGCD0103 reduces pulmonary arterial pressure more dramatically than tadalafil, a standard-of-care therapy for human pulmonary hypertension that functions as a vasodilator. Moreover, MGCD0103 improves pulmonary artery acceleration time and reduced systolic notching of the pulmonary artery flow envelope, which suggests a positive impact of the HDAC inhibitor on pulmonary vascular remodeling and stiffening. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	HDAC enzyme assay in vitro
キナーゼアッセイ	The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purified recombinant HDAC enzymes are incubated with MGCD0103 diluted in various concentrations for 10 minutes in assay buffer [25 mM HEPES (pH 8.0), 137 mM NaCl, 1 mM MgCl₂, 2.7 mM KCl] at room temperature. The substrate Boc-Lys(ε-Ac)-AMC is added to the reaction for further incubation at 37 °C. The concentration of the substrate and the incubation time varies for different isotypes of HDAC enzymes. A 20-min trypsin incubation at room temperature allows the release of the fluorophore from the deacetylated substrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of 470 nm, and cutoff at 435 nm.
細胞アッセイ	細胞株	Human mammary epithelial cells (HMEC), human foreskin fibroblasts (MRHF) cells
	濃度	0-60 μM
	反応時間	72 hours
	実験の流れ	Human mammary epithelial cells (HMEC) and human foreskin fibroblasts (MRHF) cells in 96-well plates are incubated with MGCD0103 at various concentrations for 72 hours at 37 °C in 5% CO₂. MTT is added at a final concentration of 0.5 mg/ml and incubated with the cells for 4 hours before an equal volume of solubilization buffer [50% N,N-dimethylformamide, 20% SDS (pH 4.7)] is added. After overnight incubation, solubilized dye is quantified by reading at 570 nm using a reference at 630 nm. Absorbance values are converted to cell numbers according to a standard growth curve of the relevant cell line. The concentration which reduces cell numbers to 50% relative to DMSO-treated cells is determined as MTT IC5
動物実験	動物モデル	Female CD-1 nude mice bearing H1437 tumors
	投薬量	80 mg/kg
	投与方法	Administered via p.o.

参考

カスタマーフィードバック

: Data from [Oncogene, 2012, 32, 3896-903]

: Data from [PLoS One, 2012, 7, e52095]

: Data from [J Biol Chem, 2011, 286, 23842–23851]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Romidepsin and afatinib abrogate JAK-STAT signaling and elicit synergistic antitumor effects in cutaneous T-cell lymphoma [ J Invest Dermatol, 2024, S0022-202X(23)03210-4]	PubMed: 38219917
Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation [ Clin Epigenetics, 2024, 16(1):13]	PubMed: 38229153
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051]	PubMed: 37598220
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051]	PubMed: 37598220
Genotype-Tailored ERK/MAPK Pathway and HDAC Inhibition Rewires the Apoptotic Rheostat to Trigger Colorectal Cancer Cell Death [ Mol Cancer Ther, 2023, 22(1):52-62]	PubMed: 36343387
CSE1L is a negative regulator of the RB-DREAM pathway in p53 wild-type NSCLC and can be targeted using an HDAC1/2 inhibitor [ Sci Rep, 2023, 13(1):16271]	PubMed: 37759078
Phosphorylation of TGIF2 represents a therapeutic target that drives EMT and metastasis of lung adenocarcinoma [ BMC Cancer, 2023, 23(1):52]	PubMed: 36647029
Hdac1-deficiency affects the cell cycle axis Cdc25-Cdk1 causing impaired G2/M phase progression and reduced cardiomyocyte proliferation in zebrafish [ Biochem Biophys Res Commun, 2023, 665:98-106]	PubMed: 37149988
HDAC Inhibitors Alleviate Uric Acid-Induced Vascular Endothelial Cell Injury by Way of the HDAC6/FGF21/PI3K/AKT Pathway [ J Cardiovasc Pharmacol, 2023, 81(2):150-164]	PubMed: 36607630
HDAC Inhibitors Alleviate Uric Acid-Induced Vascular Endothelial Cell Injury by Way of the HDAC6/FGF21/PI3K/AKT Pathway [ J Cardiovasc Pharmacol, 2023, 81(2):150-164]	PubMed: 36607630

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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