IACS-010759

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

IACS-010759 (IACS010759) 是一种线粒体氧化磷酸化 (OXPHOS) 的小分子抑制剂。

IACS-010759 (IACS010759) is a small molecule inhibitor of mitochondrial oxidative phosphorylation (OXPHOS), targets complex I of the mitochondrial electron transport chain; decreases cell viability and increases apoptosis with EC50 values between 1 nM-50 nM across multiple lines; robustly inhibits proliferation and induces apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, reduces aspartate production that leads to impaired nucleotide biosynthesis; potently inhibits tumor growth of brain cancer and AML in vivo.Blood Cancer Phase 1 Clinical(In Vitro):IACS-010759 (10, 30, 100?nM; for 4 or 5 days) reduces viability and induces apoptosis in primary AML.IACS-010759 (0.001, 0.01, 0.1, 1, 10, 100, 1000 nM; 72 hurs) robustly inhibits both OCR and galactose-dependent H460 cell viability and has nearly identical IC50 values of 1.4?nM.IACS-010759 is similarly active in mouse (average IC50?=?5.6?nM), rat (IC50?=?12.2?nM), and cynomolgus monkey (IC50?=?8.7?nM) cell lines.IACS-010759 (0.01-10 μM) yieldes a maximal reduction of growth of?>?50% in the majority of cancer cell lines (24 of 30 pancreatic (PDAC), 19 of 20 ovarian, 13 of 16 triple-negative breast (TNBC), 8 of 10 non-small-cell lung (NSCLC)) and a subset (11of 30 PDAC, 10 of 20 ovarian, 5 of 16 TNBC, 2 of 10 NSCLC) exhibited?>?100% growth inhibition. (In Vivo):IACS-010759 (5, 10, 25?mg/kg/day; oral; for 21 d) results in tumor regression with minimal body weight loss at the 5 or 10?mg/kg dose in mice bearing NB-1 (PGD-null) subcutaneous xenografts. IACS-010759 at the 25?mg/kg dose is not tolerated.IACS-010759 HCl (10?mg/kg; orally; QD (daily) or QD×5 (5 d on/2 d off); for 35 d) increases median survival from 28 d to longer than 60 d, whereas less-frequent dosing schedules (Q2D or Q3D) enhances survival to a lesser extent.IACS-010759 (0.3?mg/kg for iv; 1?mg/kg for oral) has low plasma clearance with a high volume of distribution, resulting in a prolonged terminal half-life (>24?h).

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IACS010759

Others

Other Targets

complexIofoxidativephosphorylation

Cancer

Blood cancer

1570496-34-2

562.568

C25H25F3N6O4S

>98% (HPLC)

DMSO: 30 mg/mL), 53.3 mM （ < 1 mg/ml refers to the product slightly soluble or insoluble )

CC1=NC(=NN1CC2=CC(=CC=C2)N3CCC(CC3)S(=O)(=O)C)C4=NC(=NO4)C5=CC=C(C=C5)OC(F)(F)F

5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole

(-20℃)

With Ice Pack

≥ 2 years