Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0353)
Name
Imidazole ketone erastin
Synonyms
Imidazole ketone erastin; 1801530-11-9; IKE; PUN30119; Imidazole ketone erastinIKE; CHEMBL3629671; 3-(5-(2-(1H-imidazol-1-yl)acetyl)-2-isopropoxyphenyl)-2-((4-(2-(4-chlorophenoxy)acetyl)piperazin-1-yl)methyl)quinazolin-4(3H)-one; SCHEMBL16924899; BCP31858; BXC53011; EX-A3112; BDBM50126162; NSC819610; s8877; ZB1594; AKOS037648788; Ferroptosis inducer IKE; PUN-30119; NSC-819610; AC-35771; BS-15620; HY-114481; CS-0086985; D70076; IKE; Ferroptosis inducer IKE; PUN30119; PUN-30119; PUN 30119; 2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(2-imidazol-1-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C35H35ClN6O5
IUPAC Name
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(2-imidazol-1-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one
Canonical SMILES
CC(C)OC1=C(C=C(C=C1)C(=O)CN2C=CN=C2)N3C(=NC4=CC=CC=C4C3=O)CN5CCN(CC5)C(=O)COC6=CC=C(C=C6)Cl
InChI
InChI=1S/C35H35ClN6O5/c1-24(2)47-32-12-7-25(31(43)20-40-14-13-37-23-40)19-30(32)42-33(38-29-6-4-3-5-28(29)35(42)45)21-39-15-17-41(18-16-39)34(44)22-46-27-10-8-26(36)9-11-27/h3-14,19,23-24H,15-18,20-22H2,1-2H3
InChIKey
PSPXJPWGVFNGQI-UHFFFAOYSA-N
PubChem CID
91824786
Full List of Ferroptosis Target Related to This Drug
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Diffuse large B-cell lymphoma ICD-11: 2A81
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model SU-DHL-1 cells Anaplastic large cell lymphoma Homo sapiens CVCL_0538
SU-DHL-2 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_9550
SU-DHL-6 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_2206
SU-DHL-8 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_2207
SU-DHL-10 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1889
SU-DHL-16 cells B-cell non-Hodgkin lymphoma Homo sapiens CVCL_1890
A3/Kawakami cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1062
OCI-LY8 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_8803
U-937 cells Adult acute monocytic leukemia Homo sapiens CVCL_0007
DoHH2 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1179
HBL-1 cells Non-Hodgkin lymphoma Homo sapiens CVCL_M572
U-2932 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1896
SU-DHL-7 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_4380
SU-DHL-9 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_4379
A4/Fukuda cells B acute lymphoblastic leukemia Homo sapiens CVCL_1064
WSU-NHL cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1793
SU-DHL-5 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1735
Karpas-422 cells Diffuse large B-cell lymphoma Homo sapiens CVCL_1325
In Vivo Model
NOD/SCID mice (12-weeks of age and ~28 g weight) were weighed before injection and divided into groups of 3 mice per cage. Mice were dosed using three different routes, IP and PO with 50 mg/kg IKE, and IV with 17 mg/kg IKE. Samples were collected at 0, 1, 3, 4, and 8 h from three mice per time point. Additionally, three mice per group were used as controls by administration with equivalent amount of vehicle 1 by IP, PO, and IV, and samples were collected at 8 h. At the appropriate time, mice were sacrificed by CO2 asphyxiation for 3 min and ~0.5 mL of blood was collected via cardiac puncture.

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Response regulation Imidazole ketone erastin (IKE) is a potent, selective, and metabolically stable system xc- (SLC7A11)inhibitor. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model.
References
Ref 1 Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model. Cell Chem Biol. 2019 May 16;26(5):623-633.e9. doi: 10.1016/j.chembiol.2019.01.008. Epub 2019 Feb 21.