Structure of RSL3
CAS No.: 1219810-16-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
RSL3 ((1S,3R)-RSL3) is an inhibitor of glutathione peroxidase 4 (GPX4), which reduces GPX4 expression and induces ferroptosis in head and neck cancer cells. In HN3 resistant cells, it increases the protein levels of p62 and Nrf2, leading to Keap1 inactivation.
Synonyms: (1S,3R)-RSL3
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CAS No. : | 1219810-16-8 |
Formula : | C23H21ClN2O5 |
M.W : | 440.88 |
SMILES Code : | O=C([C@H]1CC2=C([C@H](C3=CC=C(C(OC)=O)C=C3)N1C(CCl)=O)NC4=C2C=CC=C4)OC |
Synonyms : |
(1S,3R)-RSL3
|
MDL No. : | MFCD30187526 |
InChI Key : | TXJZRSRTYPUYRW-NQIIRXRSSA-N |
Pubchem ID : | 1750826 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
Huh7 | 5 μM | RSL3 significantly suppressed the viability of Huh7 cells and induced ferroptosis. | PMC8458041 | |
HepG2 | 5 μM | RSL3 significantly suppressed the viability of HepG2 cells and induced ferroptosis. | PMC8458041 | |
C4-2 | 0.5 μM | 9 days | To evaluate the effect of RSL3 on prostate cancer cell colony formation, results showed that RSL3 significantly inhibited colony formation of prostate cancer cells. | PMC7969452 |
PC3 | 0.125, 0.25, 0.5 μM | 72 h | To evaluate the effect of RSL3 on prostate cancer cell growth, results showed that all prostate cancer cell lines were sensitive to RSL3-induced ferroptosis. | PMC7969452 |
DU145 | 0.125, 0.25, 0.5, 1, 2, and 4 μM | 72 h | To evaluate the effect of RSL3 on prostate cancer cell growth, results showed that all prostate cancer cell lines were sensitive to RSL3-induced ferroptosis. | PMC7969452 |
G-361 | 0.5 µM | 24 h | RSL3 induced ferroptosis in G-361 cells, and overexpression of miR-137 suppressed RSL3-induced ferroptosis | PMC6113319 |
A375 | 0.1 µM | 24 h | RSL3 induced ferroptosis in A375 cells, and overexpression of miR-137 suppressed RSL3-induced ferroptosis | PMC6113319 |
HT29 cells | 3 µM | 24 h | RSL3 induced ferroptosis by increasing ROS levels and the cellular labile iron pool, leading to cell death. | PMC6262051 |
LoVo cells | 3 µM | 24 h | RSL3 induced ferroptosis by increasing ROS levels and the cellular labile iron pool, leading to cell death. | PMC6262051 |
HCT116 cells | 3 µM | 24 h | RSL3 induced ferroptosis by increasing ROS levels and the cellular labile iron pool, leading to cell death. | PMC6262051 |
PANC1 cells | 0.5 µM | 6 h | RSL3 induced cell death and lipid peroxidation in PANC1 cells, and CQ inhibited RSL3-induced cell death and lipid peroxidation. | PMC8632302 |
HT1080 cells | 0.5 µM | 6 h | RSL3 induced cell death and lipid peroxidation in HT1080 cells, and CQ inhibited RSL3-induced cell death and lipid peroxidation. | PMC8632302 |
60 human cancer cell lines | 0.5 µM | 3 and 6 h | RSL3 exhibits wider and stronger activity in the upregulation of MAP1LC3B-II or downregulation of SQSTM1 in 80% (48/60) or 63% (38/60) of cell lines, respectively. Both RSL3 and erastin failed to affect SLC7A11 expression, but they led to GPX4 downregulation in 12% (7/60) and 3% (2/60) of cell lines, respectively. | PMC8632302 |
SH-SY5Y cells | 20 μM | To evaluate the inhibitory effect of RSL3 and erastin-induced ferroptosis in SH-SY5Y cells, it was found that ThA increased cell viability in a dose-dependent manner at concentrations of 2-16 μM. | PMC11488096 | |
PC-12 cells | 0.5 μM | 4, 8, 12, 24 h | To evaluate the inhibitory effect of RSL3-induced ferroptosis in PC-12 cells, it was found that ThA significantly increased cell survival and effectively prevented ferroptosis at all observed time points. | PMC11488096 |
Human epidermal keratinocytes (HEKa) | 10 μM | 6 h | To assess the effect of RSL3 on cell viability, results showed that RSL3 treatment significantly reduced cell viability. | PMC11735110 |
EOC 20 microglial cells | 500 nM | 5 h | To test the sensitivity to RSL3-induced ferroptosis, M1-activated cells showed high resistance to RSL3, while M0 and M2-activated cells were susceptible. | PMC7233108 |
Bone marrow-derived macrophages (BMDM) | 500 nM | 5 h | To test the sensitivity to RSL3-induced ferroptosis, M1-activated cells showed high resistance to RSL3, while M0 and M2-activated cells were susceptible. | PMC7233108 |
RAW 264.7 macrophages | 500 nM | 5 h | To test the sensitivity to RSL3-induced ferroptosis, M1-activated cells showed high resistance to RSL3, while M0 and M2-activated cells were susceptible. | PMC7233108 |
HK2 cells | 1 μM | 24 h | RSL3 induces ferroptosis in HK2 cells, leading to increased lipid peroxidation and cell death. | PMC10638610 |
HT22 mouse hippocampal neuronal cells | 80 nM | 24 hours | To evaluate the protective effect of catechol estrogens against erastin/RSL3-induced ferroptosis. Results showed that four catechol estrogens (2-OH-E1, 2-OH-E2, 4-OH-E1, and 4-OH-E2) significantly inhibited erastin/RSL3-induced cell death and reduced the accumulation of NO, ROS, and lipid-ROS. | PMC11473836 |
Pfa1 Gpx4-KO cells | 300 nM | 24 hours | To assess the sensitivity of FSP1 mutants to ferroptosis | PMC10643123 |
Pfa1 cells | 500 nM | 2 days | To identify possible mutations affecting FSP1's ferroptosis-suppressive function | PMC10643123 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
NSG (NOD-SCID-IL2R γ) male mice | Prostate cancer xenograft model | Intraperitoneal injection | 100 mg/kg | Twice per week, until the end of the experiment | To evaluate the effect of RSL3 on tumor growth in prostate cancer xenograft models, results showed that RSL3 significantly delayed tumor growth of DU145 and PC3 xenografts. | PMC7969452 |
Nude mice | Subcutaneous tumor model | Intraperitoneal injection | 15 mg/kg | Twice every other day for 20 days | Knockdown of miR-137 enhanced erastin-induced ferroptosis and inhibited tumor growth | PMC6113319 |
Mice | C57BL/6 mice | Topical application | 10 μM (120 μL) | Twice daily for 2 weeks | To evaluate the effect of RSL3 on mouse skin, results showed that RSL3 increased ferroptosis-specific oxPE species in the epidermis but did not induce psoriasis-like epidermal changes or immune cell infiltration. | PMC11735110 |
Mice | Zymosan-induced peritonitis model | Intraperitoneal injection | 40 mg/kg | Single injection, lasting 5 hours | To test the effect of RSL3 on M2 macrophages in vivo, RSL3 significantly reduced the number of M2 macrophages, while the NO donor DETA NONOate suppressed this reduction. | PMC7233108 |
Mice | AKI-CKD model | Intraperitoneal injection | 5 mg/kg | Daily for 14 days | RSL3 pretreatment significantly increased renal fibrosis and ferroptosis in AKI-CKD model mice and abrogated the anti-ferroptosis and renoprotective effects of RGFP966. | PMC10638610 |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
2.27mL 0.45mL 0.23mL |
11.34mL 2.27mL 1.13mL |
22.68mL 4.54mL 2.27mL |
Tags: RSL3 | (1S |3R)-RSL3 | RSL 3 | RSL-3 | Glutathione Peroxidase | Ferroptosis | inhibit | RSL3 | (1S |3R)-RSL3 | glutathione peroxidase 4 | GPX4 | ferroptosis | regulated cell death | p62 | Nrf2 | Keap1 | HN3-rslR cells | oxidative stress | 1219810-16-8
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