Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0241)
Name
Lactate
Synonyms
lactate; 2-hydroxypropanoate; 113-21-3; 2-Hydroxypropionate; Lactate ion, DL-; MeCH(OH)CO2 anion; Propanoic acid, 2-hydroxy-, ion(1-); 13GMT0VU0O; L-LACTIC ACID, 40% SOLN; CHEMBL1357; UNII-13GMT0VU0O; Lithium L(+)-lactate; Lithium; dl-lactate; DL lactate; DL lactic acid; DL-lactate ion; (RS)-lactate; (RS)-lactic acid; Lactate ion(1-); LACTATE ANION; LACTATE ION; Sodium; 2-hydroxy-propionate; LACTIC ACID, ION(1-); CHEBI:24996; DTXSID10873500; 2-Hydroxypropanoic acid ion(1-); JVTAAEKCZFNVCJ-UHFFFAOYSA-M; 2-hydroxypropanoic acid, ion(1-); BDBM50159794; AKOS015995352; NCGC00249038-01; AB01563159_01; Q27895931; 859046-34-7

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Structure
Formula
C3H5O3-
IUPAC Name
2-hydroxypropanoate
Canonical SMILES
CC(C(=O)[O-])O
InChI
InChI=1S/C3H6O3/c1-2(4)3(5)6/h2,4H,1H3,(H,5,6)/p-1
InChIKey
JVTAAEKCZFNVCJ-UHFFFAOYSA-M
PubChem CID
91435
Full List of Ferroptosis Target Related to This Drug
Stearoyl-CoA desaturase (SCD)
 Target Info 
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Regulator Hydroxycarboxylic acid receptor 1 (HCAR1) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response regulation Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Regulator Sterol regulatory element-binding protein 1 (SREBF1) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response regulation The monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of SREBP1 (SREBF1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 2 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 E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
In Vitro Model NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H446 cells Lung small cell carcinoma Homo sapiens CVCL_1562
NCI-H1688 cells Lung small cell carcinoma Homo sapiens CVCL_1487
Response regulation Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4.
Experiment 2 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 Mitogen-activated protein kinase 14 (MAPK14) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
In Vitro Model NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H446 cells Lung small cell carcinoma Homo sapiens CVCL_1562
NCI-H1688 cells Lung small cell carcinoma Homo sapiens CVCL_1487
Response regulation Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4.
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 [1]
Target for Ferroptosis Driver
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Regulator Hydroxycarboxylic acid receptor 1 (HCAR1) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

    Click to Show/Hide
Response regulation Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
Monocarboxylate transporter 1 (SLC16A1)
 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 Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

    Click to Show/Hide
Response regulation Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 (SLC16A1) inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
References
Ref 1 HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications. Cell Rep. 2020 Dec 8;33(10):108487. doi: 10.1016/j.celrep.2020.108487.
Ref 2 Drug-induced lactate confers ferroptosis resistance via p38-SGK1-NEDD4L-dependent upregulation of GPX4 in NSCLC cells. Cell Death Discov. 2023 May 15;9(1):165. doi: 10.1038/s41420-023-01463-5.