1360705-96-9

Basic information

• Product Name: [4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone
• Synonyms: [4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone;CID 49766530;ML 210
• CAS NO: 1360705-96-9
• Molecular Formula: C₂₂H₂₀Cl₂N₄O₄
• Molecular Weight: 475.3246
• Mol File: 1360705-96-9.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 644.7±55.0 °C(Predicted)
• Appearance: white to beige/
• Density: 1.415±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (up to 30 mg/ml)
• PKA: 4.69±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: [4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone(CAS DataBase Reference)
• NIST Chemistry Reference: [4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone(1360705-96-9)
• EPA Substance Registry System: [4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone(1360705-96-9)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 1360705-96-9(Hazardous Substances Data)

Usage

Description

ML210 (CAS 1360705-96-9) is selectively synthetic lethal to HRAS expressing cells compared to isogenic non-HRAS cells (IC50?= 7.1 nM for BJeLR (expressing HRASg12v) cells vs IC50?= 272 nM for BJeH-LT (non-HRAS expressing) cells.1?ML210 is able to inhibit glutathione peroxidase 4 (GPX4), an important selenoenzyme that protects cells from ferroptosis caused by iron catalyzed formation of free radicals from lipid peroxides.2,3?Treatment of several treatment-resistant cancer cell lines exhibiting a high mesenchymal state with ML210 resulted in selective induction of ferroptosis.3

Uses

ML 210 has been used as a glutathione peroxidase 4 (GPX4) inhibitor to induce ferroptosis in cancer cells. It has also been used as a GPX4 inhibitor to examine whether pharmacological inhibition of GPX4 altered prominin2 expression and impacted ferroptosis in adherent MCF10A and Hs578t cells.

Biochem/physiol Actions

ML 210 induces non-apoptotic cell death in tumor cells expressing the RAS oncogene.

References

1) Weiwer?et al.?(2012),?Development of small-molecule probes that selectively kill cells induced to express mutant RAS; Bioorg. Med. Chem. Lett.?22?1822 2) Yang?et al.?(2014),?Regulation of Ferroptotic Cancer Cell Death by GPX4; Cell?156?317 3) Viswanathan?et al.?(2017),?Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway; Nature?547?453

Upstream product

• 90-98-2 4,4'-Dichlorobenzophenone 
• 782-08-1 chlorobis(4-chlorophenyl)methane 
• 90-97-1 4,4'-dichlorobenzophenone 
• 3405-77-4 5-methylisoxazole 3-carboxylic acid 
• 27469-61-0 1-(4,4'-dichloro-benzhydryl)-piperazine 
• 960225-75-6 5-methyl-4-nitro-1,2-oxazole-3-carboxylic acid 

Relevant articles and documents

Development of small-molecule probes that selectively kill cells induced to express mutant RAS

Synthetic lethal screening is a chemical biology approach to identify small molecules that selectively kill oncogene-expressing cell lines with the goal of identifying pathways that provide specific targets against cancer cells. We performed a high-throughput screen of 303,282 compounds from the National Institutes of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) against immortalized BJ fibroblasts expressing HRASG12V followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRASG12V oncogene. This effort led to the identification of two novel molecular probes (PubChem CID 3689413, ML162 and CID 49766530, ML210) with nanomolar potencies and 4-23-fold selectivities, which can potentially be used for identifying oncogene-specific pathways and targets in cancer cells.