UNC0642

製品コードS7230 バッチS723002

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C29H44F2N6O2
分子量 546.7 CAS No. 1481677-78-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (182.91 mM)
Ethanol 50 mg/mL (91.45 mM)
Water 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 UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.
in vitro UNC0642 is competitive with the peptide substrate and non-competitive with the cofactor SAM. The Ki of UNC0642 is determined to be 3.7 ± 1 nM. It is more than 20,000-fold selective for G9a and GLP over 13 other methyltransferases (IC50 > 50,000 nM) and more than 2,000-fold selective over PRC2-EZH2 (IC50 > 5,000 nM). UNC0642 displays high potency (IC50 < 150 nM) in reducing cellular levels of H3K9me2, low cell toxicity (EC50 > 3,000 nM), resulting in a good separation of functional potency and cell toxicity with a tox/function ratio (which is determined by dividing the EC50 value of the observed toxicity by the IC50 value of the functional potency) of > 45 in U2OS, PC3, and PANC-1 cells. UNC0642 reduces clonogenicity in PANC-1 cells in a concentration-dependent manner while it has no effect on clonogenicity in MDA-MB-231 cells[1].
in vivo For evaluation in vivo PK properties in male Swiss Albino mice, a single intraperitoneal (IP) injection (5 mg/kg) of UNC0642 results in a plasma Cmax (maximum concentration) of 947 ng/mL and an AUC (area under the curve) of 1265 hr*ng/mL. It displays modest brain penetration with a brain/plasma ratio of 0.33[1]. A single intraperitoneal (i.p.) injection dose of 5 mg/kg of UNC0642 is sufficient to inhibit G9a activity in adult mice. UNC0642 improves the life span and weight gain of m+/pΔS−U pups, produces long-lasting activation of PWS-associated genes, is apparently well tolerated and produces no notable acute toxicity, and does not interfere with the expression of the AS-associated Ube3a gene[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MDA-MB-231, PC3, and U2OS cells
濃度 --
反応時間 48 h
実験の流れ

MDA-MB-231, PC3, and U2OS cells are cultured in RPMI with 10% FBS, PANC-1 cells in DMEM with 10% FBS. Cells are treated with inhibitors for 48 h. Cell viability assays are performed by incubating cells with 0.1 mg/mL of resazurin for 3-4 h. Resazurin reduction is monitored with 544 nm excitation, measuring fluorescence at 590 nm.
動物実験 動物モデル male Swiss Albino mice
投薬量 5 mg/kg
投与方法 i.p.

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：

Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression [ Cell Rep, 2024, 43(1):113575] PubMed: 38181788
Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines [ Cancers (Basel), 2023, 15(8)2199] PubMed: 37190128
MYCN driven oncogenesis involves cooperation with WDR5 to activate canonical MYC targets and G9a to repress differentiation genes [ bioRxiv, 2023, 2023.07.11.548643] PubMed: 37781575
The Changes of Histone Methylation Induced by Adolescent Social Stress Regulate the Resting-State Activity in mPFC [ RESEARCH, 2023, Vol 6 Article ID: 0264] PubMed: none
YAP1 maintains active chromatin state in head and neck squamous cell carcinomas that promotes tumorigenesis through cooperation with BRD4 [ Cell Rep, 2022, 39(11):110970] PubMed: 35705032
Glucagon signaling via supraphysiologic GCGR can reduce cell viability without stimulating gluconeogenic gene expression in liver cancer cells [ Cancer Metab, 2022, 10(1):4] PubMed: 35123542
Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer [ Cancers (Basel), 2022, 14(19)4883] PubMed: 36230806
Loss of a 7q gene, CUX1, disrupts epigenetic-driven DNA repair and drives therapy-related myeloid neoplasms [ Blood, 2021, blood.2020009195] PubMed: 34041524
Loss of a 7q gene, CUX1, disrupts epigenetically driven DNA repair and drives therapy-related myeloid neoplasms [ Blood, 2021, 138(9):790-805] PubMed: 34473231
SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells [ Cell Death Dis, 2021, 12(6):570] PubMed: 34108444

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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