In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml
Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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
UNC3866 is a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. This compound 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
CBX4 chromodomains
CBX7 chromodomains
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 this compound for CBX2, -4, -6 and -8 is also surprisingly well correlated with the percent sequence identity of each chromodomain relative to that of CBX7. It 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, this chemical is 65-fold selective for CBX4/7 over CDY1 and 9-fold selective for CBX4/7 over CDYL1b and CDYL2. This compound antagonises PRC1 chromodomains in cells. Though its permeability is low, it is sufficiently cell permeable and stable to evaluate its ability to engage and antagonise the functions of its chromodomain targets in cells. It inhibits PC3 cell proliferation .
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 this compound 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 this chemical at higher doses for in vivo experiments is currently under investigation.
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, this compound or this chemical. For dose-response studies, the EC50 is derived from a six-point titration ranging from 100 μM to 0.4 μM of this compound or this chemical. 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 this compound- or this chemical-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.
RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.
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.
