| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
IACS-10759 (IACS-010759) is an oxidative phosphorylation inhibitor, IACS-10759 is a potent inhibitor of complex I of oxidative phosphorylation ( OXPHOS ).
Cell lines | AML cell line |
Preparation Method | Each AML cell line was cultured in 123 nM IACS-010759 medium for 72 h. |
Reaction Conditions | 123nM IACS-010759 for 72 h |
Applications | In most cell lines, IACS-010759 treatment modestly increased apoptosis by up to twofold. |
Animal models | Mouse models of glioblastoma and/or neuroblastoma and AML |
Preparation Method | To determine whether the observed in vitro and ex vivo effects predicted in vivo responses in preclinical models at tolerated doses, IACS-010759 can be evaluated in mouse models of glioblastoma and/or neuroblastoma and AML. The PK profile of IACS-010759 was determined in mice following intravenous (0.3mg/kg) and oral (1mg/kg) administration |
Dosage form | IACS-010759 intravenous (0.3mg/kg) and oral (1mg/kg) administration |
Applications | Changes in blood glucose level with single or repeated doses of IACS-010759 did not observe. However, at 2 h after the first or fifth dose, plasma insulin levels transiently decreased and returned to control levels by 24 h postdose. |
| 产品描述 | IACS-10759 (IACS-010759) is an oxidative phosphorylation inhibitor, IACS-10759 is a potent inhibitor of complex I of oxidative phosphorylation ( OXPHOS )[1]. IACS-010759 targets glycolysis-deficient tumor cells, In most cell lines, IACS-010759 treatment modestly increased apoptosis by up to twofold[1]. IACS-010759, like known quinone-site inhibitors, suppresses chemical modification by the tosyl reagent AL1 of Asp160 in the 49-kDa subunit, located deep in the interior of a previously proposed quinone-access channel[2]. IACS-010759 in complex I is the membrane-embedded ND1 subunit because amino acid substitution at Leu55 (to Phe) in this subunit, which faces the proposed ubiquinone-access channel interior[3].Treatment of primary CLL cells with IACS-010759 greatly inhibited OxPhos but caused only minor cell death at 24 and 48 h. In the presence of stroma, the drug successfully inhibited OxPhos and diminished intracellular ribonucleotide pools[4]. Inhibition of OxPhos(by IACS-010759) induced transfer of mitochondria derived from mesenchymal stem cells (MSCs) to AML cells via tunneling nanotubes under direct-contact coculture conditions. Inhibition of OxPhos also induced mitochondrial fission and increased functional mitochondria and mitophagy in AML cells[5]. Systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes[8]. In vitro, the combination of AZD3965 and IACS-010759 is synergistic and induces DLBCL cell death, whereas monotherapy treatments induce a cytostatic response[9]. IACS-010759 also suppressed tumor growth in zebrafish and mouse xenograft models of high-risk neuroblastoma[6].Changes in blood glucose level with single or repeated doses of IACS-010759 did not observe. However, at 2 h after the first or fifth dose, plasma insulin levels transiently decreased and returned to control levels by 24 h postdose[1]. IACS-010759 as an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor-resistant intracranial melanoma xenografts and inhibited melanoma brain metastases (MBM) formation in the spontaneous MBM model[7]. References: |
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