UNC0642

Catalog No.S7230 Batch:S723002

Technical Data

Formula

C₂₉H₄₄F₂N₆O₂

Molecular Weight

546.7

CAS No.

1481677-78-4

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (182.91 mM)

Ethanol

50 mg/mL (91.45 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

1.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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.

Targets

G9a ^[1] (Cell-free assay)	GLP ^[1] (Cell-free assay)
<2.5 nM	<2.5 nM

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⁺/p^ΔS−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].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MDA-MB-231, PC3, and U2OS cells Concentrations -- Incubation Time 48 h Method 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.
Animal Study:^{^[1]}	Animal Models male Swiss Albino mice Dosages 5 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell lines
MDA-MB-231, PC3, and U2OS cells
Concentrations
--
Incubation Time
48 h
Method
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.

Animal Study:^{^[1]}

Animal Models
male Swiss Albino mice
Dosages
5 mg/kg
Administration
i.p.

References

Selleck's UNC0642 has been cited by 16 publications

MYCN drives oncogenesis by cooperating with the histone methyltransferase G9a and the WDR5 adaptor to orchestrate global gene transcription [ PLoS Biol, 2024, 22(3):e3002240]	PubMed: 38547242
Chronic hypoxia stabilizes 3βHSD1 via autophagy suppression [ Cell Rep, 2024, 43(1):113575]	PubMed: 38181788
The Changes of Histone Methylation Induced by Adolescent Social Stress Regulate the Resting-State Activity in mPFC [ Research (Wash D C), 2023, 6:0264]	PubMed: 38434244
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
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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