Disease relevance of NSC670977

• We have examined the effects of concanamycin B on the constitutive secretory pathway of the human hepatoma cell line, HepG2 [1].
• Concanamycin B, a vacuolar H(+)-ATPase specific inhibitor suppresses bone resorption in vitro [2].

High impact information on NSC670977

• We have examined trafficking of major histocompatibility complex (MHC) class II molecules in human B cells exposed to concanamycin B, a highly specific inhibitor of the vacuolar H(+)-ATPases required for acidification of the vacuolar system and for early to late endosomal transport [3].
• In the presence of concanamycin B, SDS-stable dimer formation and transport of class II molecules out of LLC are impaired [4].
• In cells exposed to 10 nM concanamycin B, transport from the endoplasmic reticulum to the Golgi occurs at normal rates, as determined by pulse-chase analysis of endoglycosidase H-sensitive product in conjunction with subcellular fractionation experiments [1].
• The macrolide antibiotic concanamycin B is a highly selective inhibitor (IC50 = 5 nM) of the H(+)-ATPases of the vacuolar system [1].
• Concanamycin B, a potent inhibitor of V-ATPase activity and of acidification of lysosomes and endosomes, strongly and reversibly inhibited fluid output from the CVC but had minimal effect on the integrity of the decorated spongiome as observed by immunofluorescence [5].

Biological context of NSC670977

• In the course of screening for compounds that induce apoptosis in EGFR-overexpressing human epidermal carcinoma A431 cells from secondary metabolites of microorganisms, we found that vacuolar-type H(+)-ATPase (V-ATPase) inhibitors, such as concanamycin B and destruxin E, induced apoptosis only when the cells were stimulated with EGF [6].
• Since acidic condition of these organelles is required for receptor recycling and hydrolysis of lipoproteins, the results demonstrate that concanamycin-B inhibition of oxidized-LDL-induced accumulation of lipid droplets and cholesteryl esters in macrophages J774 is associated with reduced ATP-dependent acidification of these organelles [7].
• Furthermore, concanamycin B suppresses the antigen presentation by MHC class II molecules [8].

Anatomical context of NSC670977

• Multinucleated osteoclastic cells were suspended on dentine slices and cultured for 48 h in the presence or absence of either concanamycin B or bafilomycin A1, specific inhibitors of vacuolar H(+)-ATPase [9].
• Concanamycin B also abrogates the enhancement of the MHC class II expression by IL-4 on mouse lymphocytes [8].
• Prodigiosin 25-C suppression of cytotoxic T cells in vitro and in vivo similar to that of concanamycin B, a specific inhibitor of vacuolar type H(+)-ATPase [10].

Associations of NSC670977 with other chemical compounds

• To clarify the participation of perforin/granzymescell mediated cytotoxicity (P/G-CMC), when EGTA or concanamycin B (CMB) was added to the cytotoxicity assays, both cytotoxicities were completely inhibited by these drugs in a dose-dependent manner [11].

Gene context of NSC670977

• We show here that concanamycin B inhibits the expression of MHC class II molecules on Colo 205 cells, whereas it does not affect the expression of MHC class I and ICAM-1 molecules [8].
• Concanamycin B was found to inhibit PTH-stimulated osteoclastic pit formation and to suppress the acidification of vacuolar organelles by V-ATPase in the osteoclasts [2].

References