EED226 | CAS#2083627-02-3 | EED inhibitor | PRC2 inhibitor

MedKoo Cat#: 407382 | Name: EED226

Description:

WARNING: This product is for research use only, not for human or veterinary use.

EED226 is a potent, selective, and orally bioavailable EED inhibitor. induces robust and sustained tumor regression in EZH2MUT preclinical DLBCL model. EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 shows similar activity to SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. EED226 inhibits PRC2 activity via an allosteric mechanism and offers an opportunity for treatment of PRC2-dependent cancers. demonstrated very impressive antitumor activities in mouse xenograft model.

Chemical Structure

EED226

CAS#2083627-02-3

Theoretical Analysis

MedKoo Cat#: 407382

Name: EED226

CAS#: 2083627-02-3

Chemical Formula: C17H15N5O3S

Exact Mass: 369.0896

Molecular Weight: 369.40

Elemental Analysis: C, 55.28; H, 4.09; N, 18.96; O, 12.99; S, 8.68

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship

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Related CAS #

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Synonym

EED226; EED-226; EED 226.

IUPAC/Chemical Name

N-(Furan-2-ylmethyl)-8-(4-(methylsulfonyl)phenyl)[1,2,4]-triazolo[4,3-c]pyrimidin-5-amine

InChi Key

DYIRSNMPIZZNBK-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H15N5O3S/c1-26(23,24)14-6-4-12(5-7-14)15-10-19-17(22-11-20-21-16(15)22)18-9-13-3-2-8-25-13/h2-8,10-11H,9H2,1H3,(H,18,19)

SMILES Code

O=S(C1=CC=C(C2=CN=C(NCC3=CC=CO3)N4C2=NN=C4)C=C1)(C)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C7R05B23

QC Data

View QC data: current batch, Lot#C7R05B23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

EED226 is a polycomb repressive complex 2 (PRC2) inhibitor, which binds to the K27me3-pocket on embryonic ectoderm development (EED).

In vitro activity:

The basal expression of PRC2-related proteins was determined in HK1, C17C, NPC43 and C666-1 cell lines, with an immortalized epithelial nasopharyngeal epithelial cell line NP69 serving as a control. EZH2 and EED are expressed in all 4 NPC cell lines, while the expression levels of EZH2 and EED in EBV-positive NPC cell lines (C17C, NPC43 and C666-1) appeared to be higher than in the EBV-negative NPC cell lines (HK1) and NP69 cells (Figure 1C). Following treatment with EED226 at 1 μM, 5 μM and 10 μM for up to 72 hours, H3K27me3 expression was significantly reduced in both C666-1 and HK1 cell lines in a dose-response relationship (Figure 1D). EED226 could significantly reduce EED expression, but the effect on EZH2 was relatively modest (Figure 1E). Using proliferating cell nuclear antigen (PCNA) as an indicator, EED226 at low concentrations could inhibit cellular proliferation in C666-1 cells, while higher concentrations of EED226 were needed to inhibit proliferation in HK1 cells (Figure 1F). Reference: Am J Cancer Res. 2020; 10(10): 3267–3284. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642668/

In vivo activity:

To further assess the effect of PRC2 inhibition by EED226 in vivo, 4 and 40 mg/kg twice-daily doses of EED226 were given to mice orally for a longer period of time, and tumor volume was measured. Both 4 and 40 mg/kg doses were well tolerated, and the 40 mg/kg dose induced complete tumor regression when dosed for 32 d (Fig. 4f,g and Supplementary Fig. 4c). In the 4 mg/kg bid dose group, tumor growth was also inhibited and reached stasis at the end of the dosing period (Fig. 4f). Thus, EED226 clearly demonstrates a dose-dependent efficacy in the mouse xenograph study. Reference: Nat Chem Biol. 2017 Apr;13(4):381-388. https://www.nature.com/articles/nchembio.2304

	Solvent	mg/mL	mM
Solubility
	DMSO	31.0	83.92
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.35
	DMF	33.0	89.33

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 369.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhu J, Li L, Tong J, Hui C, Wong CH, Lo KW, Chan R, Ai QY, Hui EP, Chan AT, To KF, Tao Q, Ma BB. Targeting the polycomb repressive complex-2 related proteins with novel combinational strategies for nasopharyngeal carcinoma. Am J Cancer Res. 2020 Oct 1;10(10):3267-3284. PMID: 33163269; PMCID: PMC7642668. 2. Turner AW, Dronamraju R, Potjewyd F, James KS, Winecoff DK, Kirchherr JL, Archin NM, Browne EP, Strahl BD, Margolis DM, James LI. Evaluation of EED Inhibitors as a Class of PRC2-Targeted Small Molecules for HIV Latency Reversal. ACS Infect Dis. 2020 Jul 10;6(7):1719-1733. doi: 10.1021/acsinfecdis.9b00514. Epub 2020 May 30. PMID: 32347704; PMCID: PMC7359025. 3. Qi W, Zhao K, Gu J, Huang Y, Wang Y, Zhang H, Zhang M, Zhang J, Yu Z, Li L, Teng L, Chuai S, Zhang C, Zhao M, Chan H, Chen Z, Fang D, Fei Q, Feng L, Feng L, Gao Y, Ge H, Ge X, Li G, Lingel A, Lin Y, Liu Y, Luo F, Shi M, Wang L, Wang Z, Yu Y, Zeng J, Zeng C, Zhang L, Zhang Q, Zhou S, Oyang C, Atadja P, Li E. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED. Nat Chem Biol. 2017 Apr;13(4):381-388. doi: 10.1038/nchembio.2304. Epub 2017 Jan 30. PMID: 28135235. 4. Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu J, Zhao K, Shultz MD, Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang J, Zhang C, Li L, Zeng J, Feng L, Zhang C, Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon MP, Atadja P, Oyang C. Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy. J Med Chem. 2017 Mar 23;60(6):2215-2226. doi: 10.1021/acs.jmedchem.6b01576. Epub 2017 Feb 6. PMID: 28092155.

In vitro protocol:

In vivo protocol:

1. Qi W, Zhao K, Gu J, Huang Y, Wang Y, Zhang H, Zhang M, Zhang J, Yu Z, Li L, Teng L, Chuai S, Zhang C, Zhao M, Chan H, Chen Z, Fang D, Fei Q, Feng L, Feng L, Gao Y, Ge H, Ge X, Li G, Lingel A, Lin Y, Liu Y, Luo F, Shi M, Wang L, Wang Z, Yu Y, Zeng J, Zeng C, Zhang L, Zhang Q, Zhou S, Oyang C, Atadja P, Li E. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED. Nat Chem Biol. 2017 Apr;13(4):381-388. doi: 10.1038/nchembio.2304. Epub 2017 Jan 30. PMID: 28135235. 2. Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu J, Zhao K, Shultz MD, Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang J, Zhang C, Li L, Zeng J, Feng L, Zhang C, Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon MP, Atadja P, Oyang C. Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy. J Med Chem. 2017 Mar 23;60(6):2215-2226. doi: 10.1021/acs.jmedchem.6b01576. Epub 2017 Feb 6. PMID: 28092155.

1: Targeting the EED-H3K27me3 Interaction Allosterically Inhibits PRC2. Cancer Discov. 2017 Feb 13. doi: 10.1158/2159-8290.CD-RW2017-030. [Epub ahead of print] PubMed PMID: 28193775. 2: Qi W, Zhao K, Gu J, Huang Y, Wang Y, Zhang H, Zhang M, Zhang J, Yu Z, Li L, Teng L, Chuai S, Zhang C, Zhao M, Chan H, Chen Z, Fang D, Fei Q, Feng L, Feng L, Gao Y, Ge H, Ge X, Li G, Lingel A, Lin Y, Liu Y, Luo F, Shi M, Wang L, Wang Z, Yu Y, Zeng J, Zeng C, Zhang L, Zhang Q, Zhou S, Oyang C, Atadja P, Li E. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED. Nat Chem Biol. 2017 Apr;13(4):381-388. doi: 10.1038/nchembio.2304. Epub 2017 Jan 30. PubMed PMID: 28135235. 3: Huang Y, Zhang J, Yu Z, Zhang H, Wang Y, Lingel A, Qi W, Gu J, Zhao K, Shultz MD, Wang L, Fu X, Sun Y, Zhang Q, Jiang X, Zhang J, Zhang C, Li L, Zeng J, Feng L, Zhang C, Liu Y, Zhang M, Zhang L, Zhao M, Gao Z, Liu X, Fang D, Guo H, Mi Y, Gabriel T, Dillon MP, Atadja P, Oyang C. Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy. J Med Chem. 2017 Mar 23;60(6):2215-2226. doi: 10.1021/acs.jmedchem.6b01576. Epub 2017 Feb 6. PubMed PMID: 28092155. 4: Li L, Zhang H, Zhang M, Zhao M, Feng L, Luo X, Gao Z, Huang Y, Ardayfio O, Zhang JH, Lin Y, Fan H, Mi Y, Li G, Liu L, Feng L, Luo F, Teng L, Qi W, Ottl J, Lingel A, Bussiere DE, Yu Z, Atadja P, Lu C, Li E, Gu J, Zhao K. Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED. PLoS One. 2017 Jan 10;12(1):e0169855. doi: 10.1371/journal.pone.0169855. eCollection 2017 Jan 10. PubMed PMID: 28072869; PubMed Central PMCID: PMC5224880.

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Description:

Chemical Structure

Theoretical Analysis

Price and Availability

Preparing Stock Solutions

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