Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0003)
Name
Ascorbic Acid
Synonyms
l-ascorbic acid; ascorbic acid; vitamin C; 50-81-7; L(+)-Ascorbic acid; L-ascorbate; Ascoltin; ascorbate; Ascorbicap; Cevitamic acid; Hybrin; Laroscorbine; Testascorbic; Allercorb; Ascorbajen; Ascorbutina; Ascorteal; Ascorvit; Cantaxin; Cebicure; Cegiolan; Celaskon; Cenetone; Cenolate; Cescorbat; Cetemican; Cevatine; Cevitamin; Citriscorb; Colascor; Concemin; Lemascorb; Proscorbin; Roscorbic; Viforcit; Viscorin; Vitacimin; Vitamisin; Vitascorbol; Adenex; Ascorb; Ascorin; Cantan; Cebion; Cebione; Ceglion; Cemagyl; Cemill; Cereon; Cergona; Cetamid; Cevalin; Cevimin; Cevital; Cevitan; Cevitex; Ciamin; Redoxon; Ribena; Vicelat; Vitace; Vitacee; Vitacin; Cebid; Cecon; Celin; Cevex; Cipca; Hicee; Xitix; Davitamon C; Arco-cee; Planavit C; Catavin C; Ce lent; Liqui-Cee; Vicomin C; Cee-Vite; Cevi-Bid; Natrascorb; Scorbacid; Scorbu-C; Secorbate; Duoscorb; C-Level; C-Vimin; Cetane-Caps TD; Cewin; Antiscorbic vitamin; C-Long; C-Quin; C-Span; Meri-C; Cee-Caps TD; L-Lyxoascorbic acid; L-Xyloascorbic acid; 3-Oxo-L-gulofuranolactone; Antiscorbutic vitamin; Ce-Mi-Lin; Natrascorb injectable; 3-Keto-L-gulofuranolactone; IDO-C; L-(+)-Ascorbic Acid; Cetane-Caps TC; Acidum ascorbinicum; CE-VI-Sol; Acidum ascorbicum; Kyselina askorbova; Dora-C-500; Ferrous ascorbate; Ascor-B.I.D.; Ascorbicab; Acide ascorbique; (R)-5-((S)-1,2-dihydroxyethyl)-3,4-dihydroxyfuran-2(5H)-one; Cortalex; Ferancee; Stuartinic; Tolfrinic; Acido ascorbico; L-Threoascorbic acid; L-3-Ketothreohexuronic acid lactone; Caswell No. 061B; Antiscorbutic factor; FEMA No. 2109; Ascorbinsaeure; Chromagen; Cetebe; Kyselina askorbova [Czech]; Ascor; L-threo-Ascorbic acid; NCI-C54808; Ascorbicum acidum; L-threo-Hex-2-enonic acid, gamma-lactone; Acide ascorbique [INN-French]; Acido ascorbico [INN-Spanish]; Acidum ascorbicum [INN-Latin]; 3-Oxo-L-gulofuranolactone (enol form); Sodascorbate; Ascorbic acid, l-; Ascorbicin; CCRIS 57; (+)-Ascorbic acid; Chewcee; Citrovit; HSDB 818; Juvamine; Vasc; UNII-PQ6CK8PD0R; PQ6CK8PD0R; Rovimix C; Scorbu C; Hex-2-enonic acid gamma-lactone, L-threo-; EINECS 200-066-2; NSC 33832; Ascorbin; Vitamin c (as ascorbic acid); Ronotec 100; Ascorbyl radical; INS NO.300; DTXSID5020106; Rontex 100; CHEBI:29073; INS-300; E-300; L-threo-hex-2-enono-1,4-lactone; L-Ascorbic acid (GMP); MFCD00064328; NSC-33832; Iron(II) ascorbate; NSC-218455; component of E and C-Level; component of Endoglobin Forte; E300; DTXCID90106; (5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2,5-dihydrofuran-2-one; component of Cortalex; component of Ferancee; NSC 218455; 6730-29-6; cevibid; NCGC00164357-01; Xyloascorbic acid, L-; Ester-C; (2R)-2-[(1S)-1,2-dihydroxyethyl]-4,5-dihydroxyfuran-3-one; (5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one; ASCORBIC ACID (II); ASCORBIC ACID [II]; L-Ascorbic acid 1000 microg/mL in Acetonitrile; 2,3-DEHYDRO-L-THREO-HEXONO-1,4-LACTONE; Ascorbinsaure; Kangbingfeng; Ceklin; ASCORBIC ACID (MART.); ASCORBIC ACID [MART.]; Acido ascorbico (INN-Spanish); Acidum ascorbicum (INN-Latin); Parentrovite; Cell C; NSC33832; vitamin-c; Viscorin 100M; (2R)-2-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2H-furan-5-one; ASCORBIC ACID (EP MONOGRAPH); ASCORBIC ACID [EP MONOGRAPH]; ASCORBIC ACID (USP MONOGRAPH); ASCORBIC ACID [USP MONOGRAPH]; Suncoat VC 40; Acid, Ascorbic; (5R)-5-((1S)-1,2-DIHYDROXYETHYL)-3,4-DIHYDROXYFURAN-2(5H)-ONE; L Ascorbic Acid; Ascorbicap (TN); Acid, L-Ascorbic; Ascoltin (TN); L-xylo-ascorbic acid; [14C]ascorbic acid; Ascorbic acid [BAN:INN:JAN]; [14C]-ascorbic acid; ascorbic acid (vit C); L-Ascorbic acid, meets USP testing specifications; DTXSID7048112; Ascorbinezuur; Cevitamate; Asorbicap; L-lyxoascorbate; L-xyloascorbate; .Ascorbinsaure; C Vitamin; 3eka; Ester C; (+)-ascorbate; L(+)-ascorbate; L-Ascorbic acid, free radical form; L-(+)-ascorbate; Ascorbic acid [USP:INN:BAN:JAN]; Vitamin C,(S); E 300; NEO-VALDRIN; Ascorbic Acid DC97SF; VIT C; Vitamin xyloascorbic acid; Prestwick3_000325; L-Ascorbic acid, 99%; ASCOR (TN); SCHEMBL785; hex-1-enofuranos-3-ulose; bmse000182; VITAMIN C [VANDF]; Vitamin C (Ascorbic acid); ASCORBIC ACID [MI]; SCHEMBL4430; ASCORBIC ACID [FCC]; ASCORBIC ACID [INN]; ASCORBIC ACID [JAN]; L-Ascorbic acid, FCC, FG; L-Ascorbic Acid, Free Acid; ASCORBIC ACID [FHFI]; ASCORBIC ACID [HSDB]; ASCORBIC ACID [INCI]; BSPBio_000329; (r)-5-(1,2-dihydroxy-ethyl)-3,4-dihydroxy-5h-furan-2-one; MLS002153776; ASCORBIC ACID [VANDF]; CHEMBL40274; L-Ascorbic acid, cell culture; L-(+)-ACSCORBIC ACID; BPBio1_000363; GTPL4532; GTPL4781; L-Ascorbic acid, reagent grade; ASCORBIC ACID [USP-RS]; ASCORBIC ACID [WHO-DD]; ASCORBIC ACID [WHO-IP]; L-Ascorbic acid, >=99.0%; CHEBI:22652; HY-B0166G; DTXCID50820452; DTXSID50986567; Ascorbic acid (JP17/USP/INN); CIWBSHSKHKDKBQ-JLAZNSOCSA-N; HMS2096A11; HMS2231N16; HMS3713A11; L-Ascorbic acid ACS reagent grade; (2R)-2-[(1S)-1,2-Dihydroxyethyl]-4,5-dihydroxy-furan-3-one; ASCORBIC ACID [ORANGE BOOK]; BCP27915; HY-B0166; L-Threoascorbic acid,Antiscorbutic factor,Vitamin C;(R)-5-((S)-1,2-Dihydroxyethyl)-3,4-dihydroxyfuran-2(5H)-one; Tox21_110315; Tox21_112104; Tox21_202127; Tox21_302958; gamma-lactone L-threo-Hex-2-enonate; HB1238; L-Ascorbic acid, analytical standard; L-Ascorbic acid, AR, >=99.5%; s3114; AKOS016843589; Tox21_112104_1; CCG-207946; DB00126; L-Ascorbic acid, mixt. with vitamin B; ACIDUM ASCORBICUM [WHO-IP LATIN]; gamma-lactone L-threo-Hex-2-enonic acid; L-Ascorbic acid, ACS reagent, >=99%; NCGC00091517-01; NCGC00091517-02; NCGC00091517-03; NCGC00091517-06; NCGC00188972-01; NCGC00256504-01; NCGC00259676-01; 53262-66-1; BP-12831; SMR001233160; L-Ascorbic acid, plant cell culture tested; L-Ascorbic acid, reagent grade, crystalline; A0537; AB00376923; Ascorbic Acid (L-Ascorbic Acid; Vitamin C); CS-0626121; SW198791-2; L-3-KETO-THREO-HEXURONIC ACID LACTONE; L-Ascorbic acid, BioUltra, >=99.5% (RT); L-Ascorbic acid, tested according to Ph.Eur.; C00072; D00018; E80759; EN300-708766; L-Ascorbic acid, p.a., ACS reagent, 99.0%; AB00376923_04; AB00376923_05; L-Ascorbic acid, JIS special grade, >=99.0%; L-Ascorbic acid, Vetec(TM) reagent grade, 99%; L-Ascorbic acid, BioXtra, >=99.0%, crystalline; Q199678; 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one; L-Ascorbic acid, puriss. p.a., >=99.0% (RT); Q27101942; 47A605F0-4187-47A8-B0CE-F9E7DA1B0076; L-Ascorbic acid, p.a., ACS reagent, reag. ISO, 99.7%; L-Threo-2,3,4,5,6-pentahydroxy-1-hexenoicacid-4-lactone; Ascorbic acid, British Pharmacopoeia (BP) Reference Standard; Ascorbic acid, European Pharmacopoeia (EP) Reference Standard; L-Ascorbic acid, certified reference material, TraceCERT(R); L-Ascorbic acid, powder, cell culture tested, gamma-irradiated; Ascorbic acid, United States Pharmacopeia (USP) Reference Standard; 4-((E)-2-[(2-HYDROXYETHYL)SULFANYL]DIAZENYL)BENZENECARBOXYLICACID; (5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one (non-preferred name); L-Ascorbic acid, anhydrous, free-flowing, Redi-Dri(TM), ACS reagent, >=99%; L-Ascorbic acid, suitable for cell culture, suitable for plant cell culture, >=98%; L-Ascorbic acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., 99.7-100.5% (oxidimetric)

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Status
Approved
Drug Type
Small molecular drug
Structure
Formula
C6H8O6
IUPAC Name
(2R)-2-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2H-furan-5-one
Canonical SMILES
C(C(C1C(=C(C(=O)O1)O)O)O)O
InChI
InChI=1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1
InChIKey
CIWBSHSKHKDKBQ-JLAZNSOCSA-N
PubChem CID
54670067
TTD Drug ID
D07AHW
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 Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model PaTu 8988t cells Pancreatic adenocarcinoma Homo sapiens CVCL_1847
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
mEFs (Mouse embryonic fibroblasts)
Panc02 cells Pancreatic ductal adenocarcinoma Mus musculus CVCL_D627
In Vivo Model
All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 105 cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm3, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days.

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Response regulation The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.
Heme oxygenase 1 (HMOX1)
 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 Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model PaTu 8988t cells Pancreatic adenocarcinoma Homo sapiens CVCL_1847
BxPC-3 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
PANC-1 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
mEFs (Mouse embryonic fibroblasts)
Panc02 cells Pancreatic ductal adenocarcinoma Mus musculus CVCL_D627
In Vivo Model
All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 105 cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm3, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days.

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Response regulation The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 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 Thyroid cancer ICD-11: 2D10
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model 8505C cells Thyroid gland anaplastic carcinoma Homo sapiens CVCL_1054
C643 cells Thyroid gland anaplastic carcinoma Homo sapiens CVCL_5969
Response regulation Vitamin C could significantly inhibit anaplastic thyroid cancer (ATC) cells growth through ferroptosis activation, evidenced by the GPX4 inactivation, ROS accumulation and iron-dependent lipid peroxidation.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model DiFi cells Colorectal carcinoma Homo sapiens CVCL_6895
CCK-81 cells Colon adenocarcinoma Homo sapiens CVCL_2873
C75 cells Colon adenocarcinoma Homo sapiens CVCL_5248
In Vivo Model
The PDX models used in this study were derived from patients (CRC0078 and CRC0121) carrying a quadruple wild-type (KRAS,NRAS,BRAF, andPIK3CA) colorectal tumor. Established tumors (average volume 300 or 500 mm3, as indicated) were treated with the following regimens, either single-agent or in combination: VitC (Sigma, 4 g/kg, intraperitoneal, daily-5 days per week), cetuximab (Merck, 10 mg/kg, intraperitoneal, twice weekly).

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Response regulation Cetuximab blunts carbohydrate metabolism by blocking glucose uptake and glycolysis, beyond promoting slow but progressive ROS production. In parallel, Vitamin C disrupts iron homeostasis and further increases ROS levels ultimately leading to ferroptosis. Considering that high-dose VitC is known to be safe in cancer patients, this findings might have clinical impact on colorectal cancer patients treated with anti-EGFR therapies.
References
Ref 1 Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway. Oxid Med Cell Longev. 2022 Jul 19;2022:5361241. doi: 10.1155/2022/5361241. eCollection 2022.
Ref 2 Vitamin C induces ferroptosis in anaplastic thyroid cancer cells by ferritinophagy activation. Biochem Biophys Res Commun. 2021 Apr 30;551:46-53. doi: 10.1016/j.bbrc.2021.02.126. Epub 2021 Mar 11.
Ref 3 Vitamin C Restricts the Emergence of Acquired Resistance to EGFR-Targeted Therapies in Colorectal Cancer. Cancers (Basel). 2020 Mar 14;12(3):685. doi: 10.3390/cancers12030685.