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Chemical Structure| 1219810-16-8 Chemical Structure| 1219810-16-8

Structure of RSL3
CAS No.: 1219810-16-8

Chemical Structure| 1219810-16-8

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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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Product Details of RSL3

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

Safety of RSL3

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

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

Protocol

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

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