tr1

TbPTR1 inhibitor 2 is identified as a new development of improved pteridine reductase-1 (PTR1) inhibitors and anti-trypanosomatidic agents[1].

TR antagonist 1 is a highly potent thyroid hormone receptor (TR) antagonist (IC50 of 36 and 22 nM for TRα and TRβ, respectively) that can be used to study diseases caused by endocrine abnormalities.

Resolvin conjugate in tissue regeneration 1 (RCTR1) is a specialized pro-resolving mediator (SPM) biosynthesized from docosahexaenoic acid by isolated human macrophages and apoptotic polymorphonuclear (PMN) neutrophils.1It has been found in human spleen and bone marrow.2RCTR1 is produced via lipoxygenase-mediated oxidation of DHA to 7(S)-8-epoxy-17(S)-HDHA, which is conjugated to glutathione.1,2,3RCTR1 (10 nM) increases phagocytosis ofE. colior apoptotic neutrophils in isolated human monocyte-derived macrophages.2It decreases chemotaxis induced by leukotriene B4in isolated human neutrophils when used at a concentration of 10 nM. RCTR1 (1 and 10 nM) accelerates tissue regeneration in planaria. Intraperitoneal administration of RCTR1 (100 ng/animal) shortens the inflammatory resolution period and decreases inflammatory exudate neutrophil infiltration in a mouse model ofE. coli-induced peritonitis. 1.Dalli, J., Ramon, S., Norris, P.C., et al.Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathwaysFASEB J.29(5)2120-2136(2015) 2.de la Rosa, X., Norris, P.C., Chiang, N., et al.Identification and complete stereochemical assignments of the new resolvin conjugates in tissue regeneration in human tissues that stimulate proresolving phagocyte functions and tissue regenerationAm. J. Pathol.188(4)950-966(2018) 3.Rodriguez, A.R., and Spur, B.W.First total synthesis of pro-resolving and tissue-regenerative resolvin sulfido-conjugatesTetrahedron Lett.58(16)1662-1668(2017)

TbPTR1 inhibitor 1 (compound 5d) is an effective inhibitor of kinetochore pteridine reductase 1 (PTR1). The IC50 of TbPTR1 inhibitor 1 inhibits Trypanosoma brucei PTR1 (TbPTR1) is <0.1 nM, EC50 of TbPTR1 inhibitor 1 inhibits Trypanosoma brucei is 0.66 μM.

Maresin conjugates in tissue regeneration 1 (MCTR1) is a specialized pro-resolving mediator (SPM) synthesized from docosahexaenoic acid in macrophages at the site of inflammation. DHA is oxidized to maresin 1 , which is then converted to MCTR1 by glutathione S-transferase Mu 4 or leukotriene C4 synthase. MCTR1 accelerates tissue regeneration in planaria (1 and 100 nM). Pretreatment with MCTR1 (50 ng/mouse, i.p.) prior to E. coli administration reduces neutrophil infiltration, shortens the inflammatory resolution period, and increases phagocytosis of E. coli by macrophages. When administered at a dose of 100 ng 12h post E. coli infection in a mouse model of peritonitis, MCTR1 reduces the amount of eicosanoids in the exudate.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a specialized pro-resolving mediator (SPM) synthesized from docosahexaenoic acid . DHA is oxidized to 16S,17S-epoxy-protectin, which is then converted to PCTR1 by glutathione S-transferase. PCTR1 levels increase during resolution of acute microbial-induced peritonitis in mice. PCTR1 (30 ng, i.p.) administration 12 hours post-infection increases macrophage numbers and activity and shortens the resolution phase of inflammation by 57%. It also reduces the levels of PGE2 , PGD2 , and TXB2 in peritoneal exudates.