Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0318)
Name
I-BET151
Synonyms
1300031-49-5; I-BET151; GSK1210151A; I-BET151 (GSK1210151A); 7-(3,5-Dimethylisoxazol-4-yl)-8-methoxy-1-((R)-1-(pyridin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one; 7-(3,5-Dimethyl-4-isoxazolyl)-1,3-dihydro-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-2H-imidazo[4,5-c]quinolin-2-one; GSK1210151A (I-BET151); CHEMBL2017291; (R)-7-(3,5-dimethylisoxazol-4-yl)-8-methoxy-1-(1-(pyridin-2-yl)ethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one; 7-(3,5-Dimethyl-1,2-oxazol-4-yl)-8-methoxy-1-[(1R)-1-(pyridin-2-yl)ethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one; 7-(3,5-Dimethyl-1,2-Oxazol-4-Yl)-8-Methoxy-1-[(1r)-1-(Pyridin-2-Yl)ethyl]-1h,2h,3h-Imidazo[4,5-C]quinolin-2-One; 7-(3,5-dimethyl-1,2-oxazol-4-yl)-8-methoxy-1-[(1R)-1-pyridin-2-ylethyl]-3H-imidazo[4,5-c]quinolin-2-one; I-BET 151; 3zyu; 4alg; 1GH; MLS006011182; GTPL7518; SCHEMBL1906755; CHEBI:95083; I-BET-151; DTXSID10680599; BCP03612; EX-A1561; BDBM50380682; MFCD22124472; NSC767599; s2780; AKOS016004407; BCP9000734; CS-0930; NSC-767599; GSK1210151A/I-BET 151; NCGC00344588-01; NCGC00344588-04; NCGC00344588-08; NCGC00344588-15; 7-(3,5-Dimethyl-4-isoxazolyl)-1,3-dihydro-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-2H-imidazo[4,5-c]q; 7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-(2-pyridinyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one; AC-27406; HY-13235; SMR004702951; BCP0726000180; SW219264-1; C72196; J-519026; Q27078015; (r)-7-(3,5-dimethyl isoxazol-4-yl)-8-methoxy-1-(1-(pyridin-2-yl)ethyl)-1,3-dihydro-2h-imidazo[4,5-c]quinolin-2-one; 2H-Imidazo[4,5-c]quinolin-2-one, 7-(3,5-dimethyl-4-isoxazolyl)-1,3-dihydro-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-; 7-(dimethyl-1,2-oxazol-4-yl)-8-methoxy-1-[(1R)-1-(pyridin-2-yl)ethyl]-1H,2H,3H-imidazo[4,5-c]quinolin-2-one

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Structure
Formula
C23H21N5O3
IUPAC Name
7-(3,5-dimethyl-1,2-oxazol-4-yl)-8-methoxy-1-[(1R)-1-pyridin-2-ylethyl]-3H-imidazo[4,5-c]quinolin-2-one
Canonical SMILES
CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)C(C)C5=CC=CC=N5)OC
InChI
InChI=1S/C23H21N5O3/c1-12-21(14(3)31-27-12)16-9-18-15(10-20(16)30-4)22-19(11-25-18)26-23(29)28(22)13(2)17-7-5-6-8-24-17/h5-11,13H,1-4H3,(H,26,29)/t13-/m1/s1
InChIKey
VUVUVNZRUGEAHB-CYBMUJFWSA-N
PubChem CID
52912189
Full List of Ferroptosis Target Related to This Drug
Unspecific Target
In total 4 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Regulator Bromodomain-containing protein 4 (BRD4) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
SK-BR-3 cells Breast adenocarcinoma Homo sapiens CVCL_0033
In Vivo Model
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.

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Response regulation BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Regulator Bromodomain-containing protein 2 (BRD2) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
SK-BR-3 cells Breast adenocarcinoma Homo sapiens CVCL_0033
In Vivo Model
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.

    Click to Show/Hide
Response regulation BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Regulator Bromodomain-containing protein 3 (BRD3) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
SK-BR-3 cells Breast adenocarcinoma Homo sapiens CVCL_0033
In Vivo Model
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.

    Click to Show/Hide
Response regulation BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes.
Experiment 4 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Regulator Bromodomain testis-specific protein (BRDT) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 cells Breast adenocarcinoma Homo sapiens CVCL_0419
SK-BR-3 cells Breast adenocarcinoma Homo sapiens CVCL_0033
In Vivo Model
Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days.

    Click to Show/Hide
Response regulation BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes.
References
Ref 1 NR5A2 synergizes with NCOA3 to induce breast cancer resistance to BET inhibitor by upregulating NRF2 to attenuate ferroptosis. Biochem Biophys Res Commun. 2020 Sep 17;530(2):402-409. doi: 10.1016/j.bbrc.2020.05.069. Epub 2020 Jun 11.