RSL-3

RSL-3 is an inhibitor of glutathione peroxidase 4 (GPX4) (ferroptosis activator), reduces the expression of GPX4 protein, and induces ferroptotic death of head and neck cancer cell. RSL-3 increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells.

Product information

CAS Number: 1219810-16-8

Molecular Weight: 440.88

Formula: C23H21ClN2O5

Synonym:

RSL 3

RSL3

RSL-3

Chemical Name: Methyl(1S,3R)-2-(2-chloroacetyl)-1-(4-(methoxycarbonyl)phenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate

Smiles: COC(=O)[C@H]1CC2=C(NC3=CC=CC=C32)[C@H](C2C=CC(=CC=2)C(=O)OC)N1C(=O)CCl

InChiKey: TXJZRSRTYPUYRW-NQIIRXRSSA-N

InChi: InChI=1S/C23H21ClN2O5/c1-30-22(28)14-9-7-13(8-10-14)21-20-16(15-5-3-4-6-17(15)25-20)11-18(23(29)31-2)26(21)19(27)12-24/h3-10,18,21,25H,11-12H2,1-2H3/t18-,21+/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

RSL-3 (0-8 μM, 72 hours) potently reduces the viability of HN3 cells, with IC50s of 0.48 µM in HN3 and 5.8 µM in HN3-rslR cells, respectively. RSL-3 (0-8 μM, 24 hours) reduces the expression of GPX4 protein, increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells.

In Vivo:

RSL-3 (100 mg/kg, Intratumorally twice per week for 20 days) significantly inhibits the growth of tumor in combination with trigonelline in mice bearing HN3R cells.

References:

1. Torii S, Shintoku R, Kubota C, Yaegashi M, Torii R, Sasaki M, Suzuki T, Mori M, Yoshimoto Y, Takeuchi T, Yamada K. An essential role for functional lysosomes in ferroptosis of cancer cells. Biochem J. 2016 Mar 15;473(6):769-77. doi: 10.1042/BJ20150658. PubMed PMID: 26759376.
2. Schoeneberger H, Belz K, Schenk B, Fulda S. Impairment of antioxidant defense via glutathione depletion sensitizes acute lymphoblastic leukemia cells for Smac mimetic-induced cell death. Oncogene. 2015 Jul 30;34(31):4032-43. doi: 10.1038/onc.2014.338. PubMed PMID: 25381820.
3. Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008 Mar;15(3):234-45. doi: 10.1016/j.chembiol.2008.02.010. PubMed PMID: 18355723; PubMed Central PMCID: PMC2683762.

Products are for research use only. Not for human use.