Scandura, Grazia;Giallongo, Cesarina;Puglisi, Fabrizio;Romano, Alessandra;Parrinello, Nunziatina Laura;Zuppelli, Tatiana;Longhitano, Lucia;Giallongo, Sebastiano;Di Rosa, Michelino;Musumeci, Giuseppe;Motterlini, Roberto;Foresti, Roberta;Palumbo, Giuseppe Alberto;Li Volti, Giovanni;Di Raimondo, Francesco;Tibullo, Daniele published 《TLR4 Signaling and Heme Oxygenase-1/Carbon Monoxide Pathway Crosstalk Induces Resiliency of Myeloma Plasma Cells to Bortezomib Treatment》 in 2022. The article was appeared in 《Antioxidants》. They have made some progress in their research.Computed Properties of C15H17ClFNO4S The article mentions the following:
Relapse in multiple myeloma (MM) decreases therapy efficiency through unclear mechanisms of chemoresistance. Since our group previously demonstrated that heme oxygenase-1 (HO-1) and Toll-like receptor 4 (TLR4) are two signaling pathways protecting MM cells from the proteasome inhibitor bortezomib (BTZ), we here evaluated their cross-regulation by a pharmacol. approach. We found that cell toxicity and mitochondrial depolarization by BTZ were increased upon inhibition of HO-1 and TLR4 by using tin protoporphyrin IX (SnPP) and TAK-242, resp. Furthermore, the combination of TAK-242 and BTZ activated mitophagy and decreased the unfolded protein response (UPR) survival pathway in association with a downregulation in HO-1 expression. Notably, BTZ in combination with SnPP induced effects mirroring the treatment with TAK-242/BTZ, resulting in a blockade of TLR4 upregulation. Interestingly, treatment of cells with either hemin, an HO-1 inducer, or supplementation with carbon monoxide (CO), a byproduct of HO-1 enzymic activity, increased TLR4 expression. In conclusion, we showed that treatment of MM cells with BTZ triggers the TLR4/HO-1/CO axis, serving as a stress-responsive signal that leads to increased cell survival while protecting mitochondria against BTZ and ultimately promoting drug resistance. The experimental procedure involved many compounds, such as (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) can reduces lesion volume in a mouse model of cerebral cavernous malformations (CCMs).Computed Properties of C15H17ClFNO4S Also attenuates increased cytokine levels in a mouse sepsis model, when given in combination with ceftazidime. Cell permeable.
Reference:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics