Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0285)

Name	Erastin
Synonyms	ERASTIN; 571203-78-6; 2-[1-[4-[2-(4-chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone; 2-(1-(4-(2-(4-chlorophenoxy)acetyl)piperazin-1-yl)ethyl)-3-(2-ethoxyphenyl)quinazolin-4(3H)-one; 2-[1-[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]ethyl]-3-(2-ethoxyphenyl)quinazolin-4-one; 2-(1-(4-(2-(4-Chlorophenoxy)acetyl)-1-piperazinyl)ethyl)-3-(2-ethoxyphenyl)-4(3H)-quinazolinone; 2-(1-(4-(2-(4-Chlorophenoxy)acetyl)piperazin-1-yl)ethyl)-3-(2-ethoxyphenyl)quinazolin-4-one; MFCD09837984; ZJA3NS42T9; CHEMBL401989; SCHEMBL4457820; Erastin, >=98% (HPLC); CHEBI:94287; DTXSID80458949; EX-A295; HMS3653K21; HMS3868M03; BCP27907; WXA20378; BDBM50376126; s7242; AKOS025147365; CCG-269987; CS-1675; Erastin - CAS 571203-78-6; SB19588; NCGC00351608-10; NCGC00351608-14; AC-35446; AS-55898; HY-15763; E7781; FT-0700333; SW208651-2; C21478; E-7781; A869751; BRD-A25004090-001-01-9; BRD-A25004090-001-02-7; BRD-A25004090-001-06-8; Q27166099; 2-[1-[4-[2-(4-chlorophenoxy)-1-oxoethyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4-quinazolinone; 4(3H)-Quinazolinone, 2-[1-[4-[2-(4-chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-; Piperazine, 1-((4-chlorophenoxy)acetyl)-4-(1-(3-(2-ethoxyphenyl)-3,4-dihydro-4-oxo-2-quinazolinyl)ethyl)- Click to Show/Hide
Structure
Structure	3D MOL 2D MOL
Formula	C30H31ClN4O4
IUPAC Name	2-[1-[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]ethyl]-3-(2-ethoxyphenyl)quinazolin-4-one
Canonical SMILES	CCOC1=CC=CC=C1N2C(=O)C3=CC=CC=C3N=C2C(C)N4CCN(CC4)C(=O)COC5=CC=C(C=C5)Cl
InChI	InChI=1S/C30H31ClN4O4/c1-3-38-27-11-7-6-10-26(27)35-29(32-25-9-5-4-8-24(25)30(35)37)21(2)33-16-18-34(19-17-33)28(36)20-39-23-14-12-22(31)13-15-23/h4-15,21H,3,16-20H2,1-2H3
InChIKey	BKQFRNYHFIQEKN-UHFFFAOYSA-N
PubChem CID	11214940

Full List of Ferroptosis Target Related to This Drug

Phospholipid hydroperoxide glutathione peroxidase (GPX4)

Target Info

In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Fibrosarcoma		ICD-11: 2B53	Disease Info
Responsed Regulator	Sphingomyelin phosphodiesterase (SMPD1)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Calu-1 cells	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response regulation	Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM ( SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target				[1]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Fibrosarcoma		ICD-11: 2B53	Disease Info
Responsed Regulator	Sphingomyelin phosphodiesterase (SMPD1)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Calu-1 cells	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response regulation	Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM (SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target				[10]
Target for Ferroptosis	Suppressor
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12	Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
Response regulation	Auranofin/buthionine sulfoxime (BSO) and Erastin/BSO cotreatment alters redox homeostasis by increasing levels of Nrf2 and HO-1 and decreasing GPX4 levels. Targeting these two main ferroptotic pathways simultaneously can overcome chemotherapy resistance in hepatocellular carcinoma (HCC).

Long-chain-fatty-acid--CoA ligase 4 (ACSL4)

Target Info

In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[2]
Target for Ferroptosis	Driver
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Responsed Regulator	Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response regulation	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

Heat shock protein beta-1 (HSPB1)

Target Info

In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[3]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Responsed Regulator	Heat shock factor protein 1 (HSF1)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 ( HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target				[3]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Responsed Regulator	Heat shock factor protein 1 (HSF1)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
In Vivo Model	Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. Click to Show/Hide
Response regulation	Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.

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				[2]
Target for Ferroptosis	Suppressor
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Responsed Regulator	Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response regulation	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

Unspecific Target

In total 8 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target				[4]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Responsed Regulator	Branched-chain-amino-acid aminotransferase, mitochondrial (BCAT2)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
Cell Process	Cell autophagy
In Vitro Model	AsPC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
	H22 cells	Hepatoma	Mus musculus	CVCL_H613
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In Vivo Model	1 x 10⁶ BCAT2 overexpression and control Panc02 cancer cells were implanted subcutaneously into the right dorsal flanks of C57BL/6 mice (five mice per group), respectively. To investigate the role of combination sorafenib with sulfasalazine inducing ferroptosis, 1 x 10⁶ Panc02 were implanted subcutaneously into the right dorsal flanks of C57BL/6 mice. To generate orthotopic tumors, forty C57BL/6 mice were surgically implanted with 1 x 10⁶ H22 cells into left lobe of livers. Click to Show/Hide
Response regulation	Ferroptosis inducers (erastin, sorafenib, or sulfasalazine) activate ferritinophagy and AMPK phosphorylation, which consequently suppresses nuclear translocation of SREBP1, and inhibits the transcription of its direct target gene BCAT2. BCAT2 is a suppressor of ferroptosis by regulating intracellular glutamate levels in pancreatic ductal adenocarcinoma cells.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target				[5]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12	Disease Info
Responsed Regulator	Ceruloplasmin (CP)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
Response regulation	Erastin and RSL3 suppress ceruloplasmin expression in hepatocellular carcinoma cells. CP suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. The suppression function of ceruloplasmin in erastin- and RSL3-induced ferroptosis is dependent on FPN.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target				[6]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12	Disease Info
Responsed Regulator	GA-binding protein subunit beta-1 (GABPB1)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
Response regulation	Erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. GABPB1 and GABPB1-AS1 are attractive therapeutic targets for hepatocellular carcinoma.
Experiment 4 Reporting the Ferroptosis-centered Drug Act on This Target				[6]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12	Disease Info
Responsed Regulator	Peroxiredoxin-5, mitochondrial (PRDX5)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
Response regulation	Erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. GABPB1 and GABPB1-AS1 are attractive therapeutic targets for hepatocellular carcinoma.
Experiment 5 Reporting the Ferroptosis-centered Drug Act on This Target				[6]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12	Disease Info
Responsed Regulator	GABPB1-AS1 (IncRNA)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
Response regulation	Erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. GABPB1 and GABPB1-AS1 are attractive therapeutic targets for hepatocellular carcinoma.
Experiment 6 Reporting the Ferroptosis-centered Drug Act on This Target				[7]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Responsed Regulator	Discoidin domain-containing receptor 2 (DDR2)		Driver	Regulator Info
Pathway Response	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
	Cell adhesion molecules			hsa04514
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	SUM52PE cells	Breast carcinoma	Homo sapiens	CVCL_3425
	ZR-75-1 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	BT-474 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	BT-20 cells	Invasive breast carcinoma of no special type	Homo sapiens	CVCL_0178
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	MDA-MB-157 cells	Breast carcinoma	Homo sapiens	CVCL_0618
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
Response regulation	Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), the receptor for collagen I, is highly expressed in ferroptosis-sensitive recurrent tumor cells and human mesenchymal breast cancer cells. Erastin treatment induces DDR2 upregulation and phosphorylation, independent of collagen I. Furthermore, DDR2 knockdown in recurrent tumor cells reduces clonogenic proliferation.
Experiment 7 Reporting the Ferroptosis-centered Drug Act on This Target				[8]
Responsed Disease	Hereditary Leiomyomatosis		ICD-11: 2C90	Disease Info
Responsed Regulator	Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1 (HDDC3)		Driver	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RCC4 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0498
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	NCI-H1975 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	A673 cells	Rhabdomyosarcoma	Homo sapiens	CVCL_0080
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response regulation	Ferroptosis-inducing erastin or cystine deprivation elevates MESH1 (HDDC3), whose overexpression depletes NADPH and sensitizes clear cell renal cell carcinoma cells to ferroptosis, whereas MESH1 depletion promotes ferroptosis survival by sustaining the levels of NADPH and GSH and by reducing lipid peroxidation.
Experiment 8 Reporting the Ferroptosis-centered Drug Act on This Target				[9]
Responsed Disease	Injury of intra-abdominal organs		ICD-11: NB91	Disease Info
Responsed Regulator	Sestrin-2 (SESN2)		Suppressor	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	AML12 cells	Normal	Mus musculus	CVCL_0140
	mEFs (Mouse embryonic fibroblasts)
In Vivo Model	Six-weeks-old male ICR mice were obtained from Orient Bio (Sungnam, Korea) and acclimatized for 1 week. For Sesn2 overexpression, ICR mice were injected with the recombinant adenovirus particles (1 x 10⁹ pfu) suspended in phosphate-buffered saline with tail vein. After 48 h, phenylhydrazine (PHZ, 60 mg/kg, i.p.) was administered to induce iron accumulation and liver injury. Click to Show/Hide
Response regulation	Treatment with erastin upregulated Sesn2 mRNA levels and luciferase reporter gene activity, and erastin-mediated Sesn2 induction was transcriptionally regulated by NF-E2-related factor 2 (Nrf2). Collectively, ferroptosis-mediated Sesn2 induction is dependent on Nrf2 and plays a protective role against iron overload and ferroptosis-induced liver injury.

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				[11]
Target for Ferroptosis	Marker/Suppressor
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In Vivo Model	A total of 60 BALB/c-nu/nu nude mice (male; age, 4-6 weeks; weight, 16-22 g) were obtained from the Shanghai Laboratory Animal Co., Ltd. N5CP cells (5 x 10⁶) were suspended in 200 ul DMEM and Matrigel mixture at a ratio of 1:1. Subsequently, the mixture was injected subcutaneously into the upper right flank of 20 nude mice. After 10 days, the mice were randomly divided into four groups and were treated with CDDP (5 mg/kg/2 days), erastin (10 mg/kg/2 days), sorafenib (10 mg/kg/2 days) or PBS by intraperitoneal injection. Two days after the third injection, the mice were sacrificed and tumours were carefully removed. For the combination experiment, CDDP (1 mg/kg) and erastin (5 mg/kg) or sorafenib (3 mg/kg) were also injected three times. Click to Show/Hide
Response regulation	The potential mechanism by which sorafenib and erastin induced ferroptosis in cisplatin (CDDP)-resistant non-small cell lung cancer (NSCLC) cells may be associated with inhibition of the expression of the Nrf2 downstream target gene xCT.

References

Ref 1	Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis. Cell Death Dis. 2021 Jan 7;12(1):26. doi: 10.1038/s41419-020-03297-w.
Ref 2	SENP1 inhibition suppresses the growth of lung cancer cells through activation of A20-mediated ferroptosis. Ann Transl Med. 2022 Feb;10(4):224. doi: 10.21037/atm-21-6909.
Ref 3	HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene. 2015 Nov 5;34(45):5617-25. doi: 10.1038/onc.2015.32. Epub 2015 Mar 2.
Ref 4	Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells. Cell Death Differ. 2021 Apr;28(4):1222-1236. doi: 10.1038/s41418-020-00644-4. Epub 2020 Oct 23.
Ref 5	Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell Signal. 2020 Aug;72:109633. doi: 10.1016/j.cellsig.2020.109633. Epub 2020 Apr 10.
Ref 6	LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells. Sci Rep. 2019 Nov 7;9(1):16185. doi: 10.1038/s41598-019-52837-8.
Ref 7	DDR2 upregulation confers ferroptosis susceptibility of recurrent breast tumors through the Hippo pathway. Oncogene. 2021 Mar;40(11):2018-2034. doi: 10.1038/s41388-021-01676-x. Epub 2021 Feb 18.
Ref 8	MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis. Nat Metab. 2020 Mar;2(3):270-277. doi: 10.1038/s42255-020-0181-1. Epub 2020 Mar 9.
Ref 9	Protective effect of sestrin2 against iron overload and ferroptosis-induced liver injury. Toxicol Appl Pharmacol. 2019 Sep 15;379:114665. doi: 10.1016/j.taap.2019.114665. Epub 2019 Jul 16.
Ref 10	Redox Modulation and Induction of Ferroptosis as a New Therapeutic Strategy in Hepatocellular Carcinoma. Transl Oncol. 2020 Aug;13(8):100785. doi: 10.1016/j.tranon.2020.100785. Epub 2020 May 13.
Ref 11	Erastin/sorafenib induces cisplatin-resistant non-small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway. Oncol Lett. 2020 Jan;19(1):323-333. doi: 10.3892/ol.2019.11066. Epub 2019 Nov 7.

Ferroptosis-centered Drug Response Information

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Prof. Shuiping Liu