UNC3866

Catalog No.S8359 Batch:S835901

Technical Data

Formula	C₄₃H₆₆N₆O₈
Molecular Weight	795.02	CAS No.	1872382-47-2
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (125.78 mM)
		Ethanol	46 mg/mL (57.86 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

UNC3866 is a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K(d) of ∼100 nM for each, and is 6- to 18-fold selective as compared to seven other CBX and CDY chromodomains.

Targets

PRC1 chromodomains ^[1]	CBX4 chromodomains ^[1]	CBX7 chromodomains ^[1]
	94 nM(Kd)	97 nM(Kd)

In vitro

UNC3866 is a potent antagonist of the CBX7-H3 interaction(IC50 = 66±1.2 nM). The affinity of UNC3866 for CBX2, -4, -6 and -8 is also surprisingly well correlated with the percent sequence identity of each chromodomain relative to that of CBX7. UNC3866 is equipotent for CBX4, which is most similar to CBX7, while it is 18-, 6- and 12-fold selective for CBX4/7 over CBX2, -6 and -8, respectively. Additionally, UNC3866 is 65-fold selective for CBX4/7 over CDY1 and 9-fold selective for CBX4/7 over CDYL1b and CDYL2. UNC3866 antagonizes PRC1 chromodomains in cells. Thought the permeability of UNC3866 is low, it is sufficiently cell permeable and stable to evaluate its ability to engage and antagonize the functions of its chromodomain targets in cells. UNC3866 inhibits PC3 cell proliferation ^[1].

In vivo

UNC3866 is the predominant species in plasma at all time points tested relative to UNC4007 and shows 25% bioavailability and moderate clearance. While these PK results are promising for a peptidic compound, the use of UNC3866 in vivo may be limited because of the high circulating levels required for intracellular target engagement due to its poor cell permeability. The potential utility of UNC3866 at higher doses for in vivo experiments is currently under investigation^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines PC3 cells Concentrations 30 μM Incubation Time 24 hours Method PC3 cells are seeded at 200 cells/well into 24-well plates. Cells are allowed to adhere overnight. The media (DMEM supplemented with 10 % FBS) is then exchanged with fresh media containing DMSO, UNC3866 or UNC4219. On day three, the media are exchanged with fresh media containing DMSO, UNC3866 or UNC4219. For dose-response studies, the EC50 is derived from a six-point titration ranging from 100 μM to 0.4 μM of UNC3866 or UNC4219. At day 0, 3 or 6, cells are fixed with ice-cold methanol for 30 sec. and rehydrated with PBS. Nuclei of the cells are stained with DAPI (0.05 μg/ml) and numerated using High Content Microscopy. For dose-response studies, the cell count of UNC3866- or UNC4219-treated cells is normalized to the average cell count of DMSO-treated cells. The EC50 is calculated using the "log[inhibitor] vs. the normalized response -- Variable slope" equation in GraphPad Prism 5.
Animal Study:^{^[1]}	Animal Models swiss albino mice Dosages 10 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell lines
PC3 cells
Concentrations
30 μM
Incubation Time
24 hours
Method
PC3 cells are seeded at 200 cells/well into 24-well plates. Cells are allowed to adhere overnight. The media (DMEM supplemented with 10 % FBS) is then exchanged with fresh media containing DMSO, UNC3866 or UNC4219. On day three, the media are exchanged with fresh media containing DMSO, UNC3866 or UNC4219. For dose-response studies, the EC50 is derived from a six-point titration ranging from 100 μM to 0.4 μM of UNC3866 or UNC4219. At day 0, 3 or 6, cells are fixed with ice-cold methanol for 30 sec. and rehydrated with PBS. Nuclei of the cells are stained with DAPI (0.05 μg/ml) and numerated using High Content Microscopy. For dose-response studies, the cell count of UNC3866- or UNC4219-treated cells is normalized to the average cell count of DMSO-treated cells. The EC50 is calculated using the "log[inhibitor] vs. the normalized response -- Variable slope" equation in GraphPad Prism 5.

Animal Study:^{^[1]}

Animal Models
swiss albino mice
Dosages
10 mg/kg
Administration
i.p.

References

[1] Stuckey JI, et al. Nat Chem Biol. 2016, 12(3):180-7.

Selleck's UNC3866 has been cited by 3 publications

Asxl1 C-terminal mutation perturbs neutrophil differentiation in zebrafish [ Leukemia, 2021, 10.1038/s41375-021-01121-8]	PubMed: 33483612
Asxl1 C-terminal mutation perturbs neutrophil differentiation in zebrafish [ Leukemia, 2021, 10.1038/s41375-021-01121-8]	PubMed: 33483612
CXCR4 Regulates Temporal Differentiation via PRC1 Complex in Organogenesis of Epithelial Glands [ Int J Mol Sci, 2021, 22(2)E619]	PubMed: 33435128

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.