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Technical Data
| Formula | C17H15N5O3S |
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| Molecular Weight | 369.40 | CAS No. | 2083627-02-3 | |
| Solubility (25°C)* | In vitro | DMSO | 73 mg/mL (197.61 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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 | EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED. | ||||
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| Targets |
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| In vitro | EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. It regulates histone H3K27 methylation and PRC2 target gene expression in cells. In the in vitro enzymatic assays, EED226 inhibits PRC2 with an IC50 (half-maximal inhibitory concentration) of 23.4 nM when the H3K27me0 peptide is used as substrate and an IC50 of 53.5 nM when the mononucleosome is used as the substrate, with the stimulatory H3K27me3 added at 1 × Kact (1.0 μM). EED226 is noncompetitive with both SAM and peptide substrate. EED226 bound to EED and PRC2 complex with a 1:1 stoichiometry and Kd of 82 nM and 114 nM, respectively. EED226 does not disrupt the PRC2 complex and could still occupy its binding pocket with a SAM-competitive EZH2 inhibitor bound to PRC2. EED226 shows remarkable selectivity for PRC2 complex over 21 other protein methyltransferases, kinases and other protein classes, The only other histone methyltransferase that can be inhibited by EED226 is the EZH1-PRC2 complex. EED226 with moderate permeability leads to a dose-dependent decrease of both global H3K27me3 and H3K27me2 markers in G401 cell[1]. | ||||
| In vivo | EED226 effectively induces tumor regression in a mouse xenograft model. EED226 in a solid dispersion formulation are well tolerated in animals. EED226 clearly demonstrates a dose-dependent efficacy in the mouse xenograph study[1]. EED226 inhibits the growth of diffuse large B-cell lymphoma (DLBCL) xenografts and reduces H3K27me3 levels to a similar extent as an EZH2 inhibitor[2]. EED226 has very low in vivo and in vitro clearance and approximately 100% oral bioavailability, low volume of distribution (0.8 L/kg), reasonable terminal t1/2 (2.2 h), and moderate plasma protein binding (PPB)(14.4%). Its solubility is relatively low and with little dependency on the pH of the medium[3]. |
Protocol (from reference)
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References
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Selleck's EED226 has been cited by 22 publications
| Exposure to high-sugar diet induces transgenerational changes in sweet sensitivity and feeding behavior via H3K27me3 reprogramming [ Elife, 2023, 12e85365] | PubMed: 37698486 |
| Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis in vitro [ Open Biol, 2023, 13(1):220211] | PubMed: 36695089 |
| Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery [ Nat Commun, 2022, 13(1):4199] | PubMed: 35859152 |
| Ezh2 competes with p53 to license lncRNA Neat1 transcription for inflammasome activation [ Cell Death Differ, 2022, 10.1038/s41418-022-00992-3] | PubMed: 35568718 |
| PRC2-mediated epigenetic suppression of type I IFN-STAT2 signaling impairs antitumor immunity in luminal breast cancer [ Cancer Res, 2022, CAN-22-0736] | PubMed: 36222718 |
| Induction of senescence-associated secretory phenotype underlies the therapeutic efficacy of PRC2 inhibition in cancer [ Cell Death Dis, 2022, 13(2):155] | PubMed: 35169119 |
| Inhibition of polycomb repressive complex 2 by targeting EED protects against cisplatin-induced acute kidney injury [ J Cell Mol Med, 2022, 26(14):4061-4075] | PubMed: 35734954 |
| EZH2-mediated H3K27me3 is a predictive biomarker and therapeutic target in uveal melanoma [ Front Genet, 2022, 13:1013475] | PubMed: 36276954 |
| PRC2 Inhibitors Overcome Glucocorticoid Resistance Driven by NSD2 Mutation in Pediatric Acute Lymphoblastic Leukemia [ Cancer Discov, 2021, candisc.1771.2020] | PubMed: 34417224 |
| Loss of PRC2 subunits primes lineage choice during exit of pluripotency [ Nat Commun, 2021, 12(1):6985] | PubMed: 34848733 |
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.