Drug Information

Drug (ID: DG01659) and It's Reported Resistant Information
Name
EED226
Synonyms
EED226; 2083627-02-3; EED-226; N-(Furan-2-Ylmethyl)-8-(4-Methylsulfonylphenyl)-[1,2,4]triazolo[4,3-C]pyrimidin-5-Amine; N-(furan-2-ylmethyl)-8-(4-(methylsulfonyl)phenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine; N-(Furan-2-ylmethyl)-8-(4-(methylsulfonyl)phenyl)[1,2,4]-triazolo[4,3-c]pyrimidin-5-amine; EED 226 monohydrate; CHEMBL4065484; SCHEMBL20867769; BDBM225230; BCP19849; EX-A1724; NSC803408; s8496; AKOS030632048; CCG-268284; CS-6391; NSC-803408; SB40406; AC-29879; AS-74203; BE165158; HY-101117; J3.609.221A; A901401; N-(Furan-2-ylmethyl)-8-(4-(methylsulfonyl)phenyl)[1,2,4]-triazolo[4,3-c]pyrimidin-5-amine;MAK683; N-[(furan-2-yl)methyl]-8-(4-methanesulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine
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Structure
Target . NOUNIPROTAC [1]
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Formula
5
IsoSMILES
CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(N3C2=NN=C3)NCC4=CC=CO4
InChI
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)
InChIKey
DYIRSNMPIZZNBK-UHFFFAOYSA-N
PubChem CID
123132228
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Diffuse large B-cell lymphoma [ICD-11: 2A81]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [1]
Molecule Alteration Missense mutation
p.Y646F (c.1937A>T)
 Molecule Info 
Sensitive Disease Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model WSU-DLCL2 cells Pleural effusion Homo sapiens (Human) CVCL_1902
Toledo cells Peripheral blood Homo sapiens (Human) CVCL_3611
SU-DHL6 cells Peritoneal effusion Homo sapiens (Human) CVCL_2206
SU-DHL4 cells Peritoneal effusion Homo sapiens (Human) CVCL_0539
OCI-LY19 cells Bone marrow Homo sapiens (Human) CVCL_1878
Karpas422 cells Pleural effusion Homo sapiens (Human) CVCL_1325
GA10 cells Brain Homo sapiens (Human) CVCL_1222
DB cells Ascites Homo sapiens (Human) CVCL_1168
AZ_521 cells Small intestine Homo sapiens (Human) CVCL_2862
In Vivo Model Female athymic balb/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 LC-MS assay; Vi-CELL assay
Mechanism Description In contrast to SAM-competitive inhibitors, EED226 acts through a distinct allosteric mechanism via direct binding to the H3K27me3 pocket of EED. We further demonstrated that EED226 regulates histone H3K27 methylation and PRC2 target gene expression in cells. EED226 effectively induced tumor regression in a mouse xenograft model. Our work demonstrates that allosteric inhibition of PRC2 by targeting EED is a promising approach for developing effective cancer therapy.
Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [1]
Molecule Alteration Missense mutation
p.Y641N (c.1921T>A)
 Molecule Info 
Sensitive Disease Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model WSU-DLCL2 cells Pleural effusion Homo sapiens (Human) CVCL_1902
Toledo cells Peripheral blood Homo sapiens (Human) CVCL_3611
SU-DHL6 cells Peritoneal effusion Homo sapiens (Human) CVCL_2206
SU-DHL4 cells Peritoneal effusion Homo sapiens (Human) CVCL_0539
OCI-LY19 cells Bone marrow Homo sapiens (Human) CVCL_1878
Karpas422 cells Pleural effusion Homo sapiens (Human) CVCL_1325
GA10 cells Brain Homo sapiens (Human) CVCL_1222
DB cells Ascites Homo sapiens (Human) CVCL_1168
AZ_521 cells Small intestine Homo sapiens (Human) CVCL_2862
In Vivo Model Female athymic balb/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 LC-MS assay; Vi-CELL assay
Mechanism Description In contrast to SAM-competitive inhibitors, EED226 acts through a distinct allosteric mechanism via direct binding to the H3K27me3 pocket of EED. We further demonstrated that EED226 regulates histone H3K27 methylation and PRC2 target gene expression in cells. EED226 effectively induced tumor regression in a mouse xenograft model. Our work demonstrates that allosteric inhibition of PRC2 by targeting EED is a promising approach for developing effective cancer therapy.
Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [1]
Molecule Alteration Missense mutation
p.Y646N (c.1936T>A)
 Molecule Info 
Sensitive Disease Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model WSU-DLCL2 cells Pleural effusion Homo sapiens (Human) CVCL_1902
Toledo cells Peripheral blood Homo sapiens (Human) CVCL_3611
SU-DHL6 cells Peritoneal effusion Homo sapiens (Human) CVCL_2206
SU-DHL4 cells Peritoneal effusion Homo sapiens (Human) CVCL_0539
OCI-LY19 cells Bone marrow Homo sapiens (Human) CVCL_1878
Karpas422 cells Pleural effusion Homo sapiens (Human) CVCL_1325
GA10 cells Brain Homo sapiens (Human) CVCL_1222
DB cells Ascites Homo sapiens (Human) CVCL_1168
AZ_521 cells Small intestine Homo sapiens (Human) CVCL_2862
In Vivo Model Female athymic balb/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 LC-MS assay; Vi-CELL assay
Mechanism Description In contrast to SAM-competitive inhibitors, EED226 acts through a distinct allosteric mechanism via direct binding to the H3K27me3 pocket of EED. We further demonstrated that EED226 regulates histone H3K27 methylation and PRC2 target gene expression in cells. EED226 effectively induced tumor regression in a mouse xenograft model. Our work demonstrates that allosteric inhibition of PRC2 by targeting EED is a promising approach for developing effective cancer therapy.
Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [1]
Molecule Alteration Missense mutation
p.Y646S (c.1937A>C)
 Molecule Info 
Sensitive Disease Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model WSU-DLCL2 cells Pleural effusion Homo sapiens (Human) CVCL_1902
Toledo cells Peripheral blood Homo sapiens (Human) CVCL_3611
SU-DHL6 cells Peritoneal effusion Homo sapiens (Human) CVCL_2206
SU-DHL4 cells Peritoneal effusion Homo sapiens (Human) CVCL_0539
OCI-LY19 cells Bone marrow Homo sapiens (Human) CVCL_1878
Karpas422 cells Pleural effusion Homo sapiens (Human) CVCL_1325
GA10 cells Brain Homo sapiens (Human) CVCL_1222
DB cells Ascites Homo sapiens (Human) CVCL_1168
AZ_521 cells Small intestine Homo sapiens (Human) CVCL_2862
In Vivo Model Female athymic balb/c nude mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 LC-MS assay; Vi-CELL assay
Mechanism Description In contrast to SAM-competitive inhibitors, EED226 acts through a distinct allosteric mechanism via direct binding to the H3K27me3 pocket of EED. We further demonstrated that EED226 regulates histone H3K27 methylation and PRC2 target gene expression in cells. EED226 effectively induced tumor regression in a mouse xenograft model. Our work demonstrates that allosteric inhibition of PRC2 by targeting EED is a promising approach for developing effective cancer therapy.
References
Ref 1 An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EEDNat Chem Biol. 2017 Apr;13(4):381-388. doi: 10.1038/nchembio.2304. Epub 2017 Jan 30.

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