Concanamycin A (Folimycin) 是一种多聚环内酯类抗生素,是选择性空泡状 H+-ATP 酶 (V-ATPase) 和溶酶体酸化抑制剂,可用于研究炎症。Concanamycin A 可增强细胞毒性 T 淋巴细胞对受感染原代细胞的免疫清除,抑制来自 HIV 和猿猴免疫缺陷病毒不同分支的 Nef 等位基因,可用于研究HIV 感染。
DMI-9523 is nuclear factor NF-κB activation inhibitor. Antigen-stimulated human T lymphocytes produce significantly lower quantities of interferon-gamma and tumor necrosis factor-alpha after stimulation in vitro in the presence of DA-DKP. DA-DKP can modul
O-11 is an analog of the fully saturated, 14-carbon fatty acid myristic acid, in which the methylene group at position 11 is replaced with oxygen. It is highly effective and selective at killingTrypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, exhibiting an LD50of less than 1 μM in a cell culture assay.1,2The toxic effects of O-11 appear to be caused by its ability to inhibit the incorporation of a single myristate into the GPI anchor of the variant surface glycoprotein (VSG), a protein critical for evading the host immune response.1O-11 exhibits essentially no anti-fungal activity when assayed usingC. neoformans, but does have a minor inhibitory effect on HIV-1 replication in T-lymphocytes.3 1.Doering, T.L., Raper, J., Buxbaum, L.U., et al.An analog of myristic acid with selective toxicity for African trypanosomesScience2521851-1854(1991) 2.Doering, T.L., Lu, T., Werbovetz, K.A., et al.Toxicity of myristic acid analogs toward African trypanosomesProceedings of the National Academy of Sciences of the United States of America919735-9739(1994) 3.Langner, C.A., Lodge, J.K., Travis, S.J., et al.4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus IThe Journal of Biological Chemisty267(24)17159-17169(1992)
Padanamide A is a bacterial metabolite originally isolated from a marine Streptomyces species. It is active against five strains of P. falciparum (EC50s = 160-340 nM), is not cytotoxic to HEK293 or HepG2 human cell lines, but is cytotoxic to Jurkat T lymphocytes with an IC50 value of approximately 60 μg/ml.
Benastatin C is a polyketide synthase-derived benastatin that has been found inStreptomycesand has diverse biological activities.1,2It inhibits glutathione S-transferase (GST; IC50= 24 μg ml for the rat liver enzyme).2Benastatin C also inhibits the esterase activity of isolated porcine pancreatic lipase (IC50= 10 μg ml). It increases LPS- or concanavalin A-induced blastogenesis of isolated mouse spleen lymphocytes in a concentration-dependent manner. 1.Xu, Z., Schenk, A., and Hertweck, C.Molecular analysis of the benastatin biosynthetic pathway and genetic engineering of altered fatty acid-polyketide hybridsJ. Am. Chem. Soc.129(18)6022-6030(2007) 2.Aoyama, T., Kojima, F., Yamazaki, T., et al.Benastatins C and D, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. Production, isolation, structure determination and biological activitiesJ. Antibiot. (Tokyo)46(5)712-718(1993)
Concanamycin B is a macrolide antibiotic that selectively inhibits vacuolar type H+-ATPases, also known as V-ATPases (IC50 = 5 nM). In this way, it blocks the acidification of vacuolar organelles as well as early to late endosomal transport. Concanamycin B interferes with bone resorption and maturation of CD8 T lymphocytes. It also prevents processing of major histocompatibility complex (MHC) class II precursors in human B cells, inhibiting the expression of MHC class II molecules on the cell surface.
Tetranactin is a macrotetrolide and a monovalent cation ionophore that has been found in S. aureus and has antibacterial, insecticidal, and mitogenic activities. It exhibits an equilibrium permeability ratio 1,000-fold greater for lithium than sodium or cesium ions accross bilayer membranes at low voltages. Tetranactin inhibits the growth of Gram-positive bacteria and C. miyabeanus and R. solani fungi when used at concentrations less than 0.9 μg/ml. Tetranactin (0.5-1.5 μg per insect) dose-dependently increases the mortality of adult C. chinensis weevils up to 100% and has mitogenic activity against T. telarius when sprayed onto plants with an LC50 value of 9.2 μg/ml. It reduces IL-1β- and cAMP-induced secretion of phospholipase A2 (PLA2) from rat mesangial cells (IC50s = 43 and 33 nM, respectively). Tetranactin (50 ng/ml) suppresses the proliferation of human T lymphocytes induced by allogeneic cells and IL-2 and supresses the generation of cytotoxic T lymphocytes in mixed lymphocyte cultures. In vivo, tetranactin (10 mg/animal per day) completely inhibits the formation of experimental autoimmune uveoretinitis (EAU) in rats.