General information
CAS n°
2243462-48-6
Mechanism of action
disruption of the endoplasmic reticulum protein quality control requiring ERAD stress response independently of the canonical unfolded protein response (UPR)
Physico-chemical properties
Molecular weight: 283.11 g.mol
Experimental solubility: PBS pH7.4: 1.0 ± 0.2 µM; PBS pH7.4 10% DMSO: 5.6 ± 0.7 µM; NaCl 9/1000 with 10% cremophor EL: 284 ± 5 µM; NaCl 9/1000 with 10% solutol HS15: 939 ± 5 µM;
Probe availability
upon request
Princeps reference
Raj, S et al. (2016) Antimicrobial Agents and Chemotherapy, 60 (3), 1438-1449, DOI:10.1128/AAC.02239-15
More bibliography
NA
Other available information on the probe
Compound identified through a chemical library screening for toxicity against Aspergillus fumigatus. The initial hit was a mixture of two isomers: isomer alpha (sr7575 or (E) 1-(2,4-Dichlorophenyl)-2-(2-nitrovinyl)-1H-pyrrole) and isomer ß ((E) 1-(2,4-Dichlorophenyl)-3-(2-nitrovinyl)-1H-pyrrole). The latter was found to have lost the ability to block the fungal growth.
Metabolic stability of sr7575 on human liver microsomes at 37°C: t1/2 = 37 ± 1 min
Other information on the target
NA
Selectivity profile
KINOMEscan (DiscoveRx) @ 10µM: 14 hits out of 451 kinases tested (S-score(35) = 0.03)
In vivo data
Not evaluated
In vitro data
Growth inhibitor of various fungi (A. fumigatus, A. flavus, Candida albicans, Cryptococcus neoformans and Saccharomyces cerevisiae) on plates and liquid media at concentrations ranging from 0.6 to 10 µg/mL.
Fungistatic effect.
Toxicity
- CiToxLAB study report
Under the experimental conditions of this study, the test item, sr7575 did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium, in the absence or the presence of a rat metabolising system.
- No lethality observed after intraperitoneally injection of sr7575 (dose 100 mg/kg) in mice
Chaine SMILES
O=N(=O)/C=C/c1cccn1c2ccc(Cl)cc2Cl