Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0179)
Name
Ibrutinib
Synonyms
Ibrutinib; 936563-96-1; PCI-32765; IMBRUVICA; PCI 32765; Ibrutinib (PCI-32765); PCI-32765 (Ibrutinib); CRA-032765; (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one; Pc-32765; 1X70OSD4VX; PCI-32765-00; 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one; CHEBI:76612; PCI32765; 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one; 1-{(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}prop-2-en-1-one; 2-Propen-1-one, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)-1-piperidinyl)-; C25H24N6O2; (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.; 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)piperidin-1- yl)prop-2-en-1-one; Ibrutinib [USAN]; Ibrutinib [USAN:INN]; UNII-1X70OSD4VX; ibrutinibum; JNJ 02; Imbruvica (TN); Ibrutinib- Bio-X; 1-{(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1- yl}prop-2-en-1-one; 2-Propen-1-one, 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-; CRA 032765; Ibrutinib, Free Base; 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one; IBRUTINIB [INN]; IBRUTINIB [JAN]; IBRUTINIB [MI]; Ibrutinib (JAN/USAN); IBRUTINIB [VANDF]; IBRUTINIB [WHO-DD]; Imbruvica; PCI-32765; MLS006010041; SCHEMBL201859; GTPL6912; IBRUTINIB [ORANGE BOOK]; CHEMBL1873475; HSDB 8260; DTXSID60893450; EX-A066; XYFPWWZEPKGCCK-GOSISDBHSA-N; AMY27873; BDBM50357312; MFCD20261150; NSC800769; AKOS022185476; DB09053; EX-5960; NSC-800769; NCGC00187912-01; NCGC00187912-02; NCGC00187912-03; NCGC00187912-12; (R)-1-(3-(4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo-[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one; AC-26942; BI164531; HY-10997; SMR004701213; SW218096-2; EN300-97039; D10223; A1-01649; J-523872; Q5984881; Z1302446275; (R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-ylprop-2-en-1-one; 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one; 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)pyrazolo[3, 4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one

    Click to Show/Hide
Structure
Formula
C25H24N6O2
IUPAC Name
1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one
Canonical SMILES
C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N
InChI
InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
InChIKey
XYFPWWZEPKGCCK-GOSISDBHSA-N
PubChem CID
24821094
Full List of Ferroptosis Target Related to This Drug
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 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 Marker/Suppressor
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Responsed Regulator Tyrosine-protein kinase BTK (BTK) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model NCI-H508 cells Cecum adenocarcinoma Homo sapiens CVCL_1564
LoVo cells Colon adenocarcinoma Homo sapiens CVCL_0399
LS513 cells Cecum adenocarcinoma Homo sapiens CVCL_1386
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SW480 cells Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
SW1116 cells Colon adenocarcinoma Homo sapiens CVCL_0544
DLD-1 cells Colon adenocarcinoma Homo sapiens CVCL_0248
HT-29 cells Colon adenocarcinoma Homo sapiens CVCL_0320
Caco-2 cells Colon adenocarcinoma Homo sapiens CVCL_0025
In Vivo Model
Sixty mice were randomly divided into six groups, (1) the CRC model group (model), (2) mice with RSL3 treatment, (3) mice with Erastin treatment, (4) mice with Ibrutinib treatment, (5) mice with RSL3 and Ibrutinib treatment, and (6) Erastin and Ibrutinib group. Murine subcutaneous tumor model and xenograft tumor mouse model were established and please refer to supplemental method for details. For CRC model group, the mice were treated with PBS for two weeks. For RSL3 group, the mice were intraperitoneal injected with RSL3 (5 mg/kg daily) for two weeks. For Erastin group, the mice were intraperitoneal injected with Erastin (30 mg/kg, twice every other day) for two weeks. For Ibrutinib treatment group, mice were administered in drinking water at a concentration of 0.16 mg/ml for two weeks. Mice were also treated in combination with RSL and Ibrutinib or Erastin and Ibrutinib.

    Click to Show/Hide
Response regulation Ibrutinib inhibited BTK, which prevented Nrf2 translocating to cell nucleus and the activation of the Nrf2 dependent antioxidant genes during oxidative stress conditions and eventually enhanced the sensitivity of Colorectal cancer (CRC) cells to ferroptosis.
References
Ref 1 Ibrutinib facilitates the sensitivity of colorectal cancer cells to ferroptosis through BTK/NRF2 pathway. Cell Death Dis. 2023 Feb 23;14(2):151. doi: 10.1038/s41419-023-05664-9.