Calmasini, Fabiano B.;Alexandre, Eduardo C.;Oliveira, Mariana G.;Silva, Fabio H.;Soares, Antonio G.;Costa, Soraia K. P.;Antunes, Edson published 《Lipopolysaccharide reduces urethral smooth muscle contractility via cyclooxygenase activation》 in 2021. The article was appeared in 《Journal of Physiology and Biochemistry》. They have made some progress in their research.Reference of (R)-Ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-enecarboxylate The article mentions the following:
In the present study, we evaluated the functional and mol. effects of LPS in mouse USM in vitro, focusing on the LPS-induced TLR4-signaling pathway. Male C57BL6/JUnib and TLR4 knockout mice (TLR4 KO) were used. The USM contraction was performed in the presence of LPS (62.5-500μg/mL), indomethacin (10μM), L-NAME (100μM), and TAK 242 (1μM). The RT-PCR assay for the IL-1β, NF-kB, and COX-2 genes was also evaluated in the presence of LPS (125μg/mL) and caspase 1 inhibitor (20μM). Our results showed that LPS reduces mouse USM contraction elicited by phenylephrine and vasopressin. This LPS-induced urethral inhibitory effect was not reversed by the TLR4 inhibition or its absence in the TLR4 KO mice. Conversely, indomethacin (but not L-NAME) reversed the LPS-induced USM hypocontractility. Mol. protocols indicated upregulation of IL-1β, NF-kβ, and COX-2 mRNA upon LPS incubation, which were blunted by caspase 1 inhibition. Our data showed that LPS reduced mouse USM contraction independently of TLR4 activation, involving caspase 1 and IL1β, NF-kB, and COX-2 gene overexpression. Therefore, this alternative pathway might be a valuable target to reduce the LPS-induced urethral dysfunction under infection and inflammatory conditions. To complete the study, the researchers used (R)-Ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-enecarboxylate (cas: 243984-11-4) .
(R)-Ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-enecarboxylate(cas:243984-11-4) is a toll-like receptor 4 (TLR4) signaling inhibitor.Reference of (R)-Ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-enecarboxylate And it can inhibits LPS-induced cytokine production in vitro (IC50 values are 1.3, 1.3 and 3.2 nM for IL-6, TNFα and NO production).
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