Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0138)
Name
Betulin
Synonyms
Betulin; 473-98-3; Betulinol; Betuline; Trochol; Betulol; Lup-20(29)-ene-3b,28-diol; Betulinic alcohol; Lup-20(29)-ene-3beta,28-diol; (+)-betulin; Lup-20(30)-ene-3beta,28-diol; NSC 4644; NSC-4644; 6W70HN7X7O; CHEBI:3086; (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(Hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol; (3beta)-lup-20(29)-ene-3,28-diol; Lup-20(29)-ene-3,28-diol, (3.beta.)-; (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol; (1R,2R,5S,8R,9R,10R,13R,14R,17S,19R)-5-(hydroxymethyl)-1,2,14,18,18-pentamethyl-8-(prop-1-en-2-yl)pentacyclo[11.8.0.0^{2,10}.0^{5,9}.0^{14,19}]henicosan-17-ol; (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol; SR-05000002167; EINECS 207-475-5; lup-20(29)-ene-3 beta,28-diol; NSC4644; UNII-6W70HN7X7O; AI3-62999; NSC692218; Lup-20(29)-ene-3,28-diol, (3beta)-; Lup-20(29)-ene-3.beta.,28-diol; Lup-20(30)-ene-3.beta.,28-diol; Betulinol (obsol.); MFCD00016802; Betulin, 23; ORISTRACT BTL; CP BETULIN; BETULIN [INCI]; Betulin, >=98%; BETULIN [MI]; Prestwick3_000990; Betulinol (obsol pound(c); Betulin, analytical standard; BSPBio_001059; CHEMBL23236; SCHEMBL131739; BPBio1_001165; MEGxp0_001726; ACon1_000091; BDBM23207; FVWJYYTZTCVBKE-ROUWMTJPSA-N; DTXSID101019934; HMS2098E21; EX-A3354; HY-N0083; s4754; Lup-20(29)-ene-3 ,28-diol; AKOS005267212; Lup-20(29)-ene-3beta ,28-diol; Lup-20(30)-ene-3beta ,28-diol; CCG-208619; CS-6156; GS-3254; LMPR0106140005; NSC-692218; NCGC00168803-01; NCGC00168803-02; NCGC00168803-04; AB00513988; B0803; (3.beta.)-Lup-20(29)-ene-3,28-diol; C08618; Lup-20(29)-ene-3,28-diol, (3beta )-; A827211; Q419726; Q-100501; SR-05000002167-2; SR-05000002167-3; BRD-K64874225-001-01-3; (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3 a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-ol; (3aS,5bR,9S,11aR)-3a-(hydroxymethyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol;Betulin; 7372-31-8

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Structure
Formula
C30H50O2
IUPAC Name
(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol
Canonical SMILES
CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)O)C)CO
InChI
InChI=1S/C30H50O2/c1-19(2)20-10-15-30(18-31)17-16-28(6)21(25(20)30)8-9-23-27(5)13-12-24(32)26(3,4)22(27)11-14-29(23,28)7/h20-25,31-32H,1,8-18H2,2-7H3/t20-,21+,22-,23+,24-,25+,27-,28+,29+,30+/m0/s1
InChIKey
FVWJYYTZTCVBKE-ROUWMTJPSA-N
PubChem CID
72326
Full List of Ferroptosis Target Related to This Drug
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 [1]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease 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
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
In Vivo Model
Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.

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Response regulation The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells.
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 Lung cancer ICD-11: 2C25
 Disease 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
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
In Vivo Model
Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.

    Click to Show/Hide
Response regulation The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells.
Ferritin heavy chain (FTH1)
 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 Lung cancer ICD-11: 2C25
 Disease 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
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
In Vivo Model
Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.

    Click to Show/Hide
Response regulation The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRAS mutant non-small-cell lung cancer (NSCLC) cells.
References
Ref 1 Co-treatment of betulin and gefitinib is effective against EGFR wild-type/KRAS-mutant non-small cell lung cancer by inducing ferroptosis. Neoplasma. 2022 May;69(3):648-656. doi: 10.4149/neo_2022_211103N1568. Epub 2022 Mar 24.