| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| Targets |
GPX4/glutathione peroxidase 4
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| ln Vitro |
With IC50 values of 25 nM and 578 nM against HRASG12V-expressing and wild-type BJ blast fibroblasts, respectively, ML162 (Compound 1a) showed molar effectiveness against two HRASG12V-expressing cell lines [1]. Treatment with ML162 (8 μM; 24 hours) inactivates Keap1, raises phospho-PERK-ATF4-SESN2 pigment, and elevates p62 and Nrf2 to chemically complement HN3R and HN3-rslR expression de cells [2]. To differing degrees, ML162 causes head and neck cancer (HNC) cell death. In addition to having a lesser percentage of cisplatin reagent (HN3R) and acquired RSL3 reagent (HN3-rslR) cells, parental HN3 cells are more susceptible [2].
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| Enzyme Assay |
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 HRAS(G12V) followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRAS(G12V) 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[1].
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| Cell Assay |
Western Blot analysis [2]
Cell Types: HN3R cells Tested Concentrations: 8 μM Incubation Duration: 24 hrs (hours) Experimental Results: The expression of p62 and Nrf2 increased in chemotherapy-resistant HN3R and HN3-rslR cells. |
| References | |
| Additional Infomation |
Glutathione peroxidase 4 (GPX4) is a regulator of ferroptosis (iron-dependent, non-apoptotic cell death); its inhibition can render therapy-resistant cancer cells susceptible to ferroptosis. However, some cancer cells develop mechanisms protective against ferroptosis; understanding these mechanisms could help overcome chemoresistance. In this study, we investigated the molecular mechanisms underlying resistance to ferroptosis induced by GPX4 inhibition in head and neck cancer (HNC). The effects of two GPX4 inhibitors, (1S, 3R)-RSL3 and ML-162, and of trigonelline were tested in HNC cell lines, including cisplatin-resistant (HN3R) and acquired RSL3-resistant (HN3-rslR) cells. The effects of the inhibitors and trigonelline, as well as of inhibition of the p62, Keap1, or Nrf2 genes, were assessed by cell viability, cell death, lipid ROS production, and protein expression, and in mouse tumor xenograft models. Treatment with RSL3 or ML-162 induced the ferroptosis of HNC cells to varying degrees. RSL3 or ML-162 treatment increased the expression of p62 and Nrf2 in chemoresistant HN3R and HN3-rslR cells, inactivated Keap1, and increased expression of the phospho-PERK-ATF4-SESN2 pathway. Transcriptional activation of Nrf2 was associated with resistance to ferroptosis. Overexpression of Nrf2 by inhibiting Keap1 or Nrf2 gene transfection rendered chemosensitive HN3 cells resistant to RSL3. However, Nrf2 inhibition or p62 silencing sensitized HN3R cells to RSL3. Trigonelline sensitized chemoresistant HNC cells to RSL3 treatment in a mouse model transplanted with HN3R. Thus, activation of the Nrf2-ARE pathway contributed to the resistance of HNC cells to GPX4 inhibition, and inhibition of this pathway reversed the resistance to ferroptosis in HNC.[2]
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| Molecular Formula |
C23H22CL2N2O3S
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|---|---|
| Molecular Weight |
477.4034
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| Exact Mass |
476.072
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| Elemental Analysis |
C, 57.87; H, 4.65; Cl, 14.85; N, 5.87; O, 10.05; S, 6.72
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| CAS # |
1035072-16-2
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| PubChem CID |
3689413
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
699.3±55.0 °C at 760 mmHg
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| Flash Point |
376.7±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.630
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| LogP |
4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
31
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| Complexity |
591
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UNVKYJSNMVDZJE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H22Cl2N2O3S/c1-30-19-10-9-17(14-18(19)25)27(21(28)15-24)22(20-8-5-13-31-20)23(29)26-12-11-16-6-3-2-4-7-16/h2-10,13-14,22H,11-12,15H2,1H3,(H,26,29)
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| Chemical Name |
2-(3-chloro-N-(2-chloroacetyl)-4-methoxyanilino)-N-(2-phenylethyl)-2-thiophen-2-ylacetamide
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| Synonyms |
ML162; 1035072-16-2; ML-162; 2-[(chloroacetyl)(3-chloro-4-methoxyphenyl)amino]-N-(2-phenylethyl)-2-thien-2-ylacetamide; SMR000206941; 2-(3-chloro-N-(2-chloroacetyl)-4-methoxyanilino)-N-(2-phenylethyl)-2-thiophen-2-ylacetamide; MLS000583955; alpha-[(2-chloroacetyl)(3-chloro-4-methoxyphenyl)amino]-N-(2-phenylethyl)-2-thiopheneacetamide;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~209.47 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0947 mL | 10.4734 mL | 20.9468 mL | |
| 5 mM | 0.4189 mL | 2.0947 mL | 4.1894 mL | |
| 10 mM | 0.2095 mL | 1.0473 mL | 2.0947 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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