BAY 87-2243

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

BAY 87-2243 是一种有效的选择性缺氧诱导因子-1 (HIF-1) 抑制剂。

BAY 87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor. Phase 1.(In Vitro):BAY 87-2243 inhibits luciferase activity with a calculated IC50 value of ~0.7 nM. Hypoxic induction of the HIF target gene CA9 on protein level in HCT116luc cells is inhibited by BAY 87-2243 with an IC50 value of ~2 nM. BAY 87-2243 inhibits mitochondrial oxygen consumption measured by using the oxygen sensitive fluorescence dye LUX-MitoXpress with an IC50 value of ~10 nM. BAY-87-2243 inhibits nuclear HIF-1α protein expression. Administration of BAY-87-2243 for about 18 days significantly reduces HIF-1α protein expression as well as pimonidazole hypoxic fraction (pHF) (mean 2.4% (BAY-87-2243) vs. 17.6% (carrier), p<0.0001), and necrotic fraction (NF) (mean 9% vs. 35.6%, p=0.0002), whereas relative vascular area (RVA) and perfused vessels (PF) remained unchanged.(In Vivo):Nude mice are inoculated with H460 cells subcutaneously and after tumors have been established, animals are treated with BAY 87-2243 (0.5, 1, 2, and 4 mg/kg) for 3 weeks by daily oral gavage. BAY 87-2243 reduced tumor weight dose dependently in line with a dose-dependent reduction of the mRNA expression levels of the HIF-1 target genes CA9, ANGPTL4, and EGLN3, whereas the mRNA expression levels of hypoxia-insensitive EGLN2 gene and of HIF-1α itself are not affected by compound treatment in vivo.

BAY 87-2243 inhibits luciferase activity with a calculated IC50 value of ~0.7 nM. Hypoxic induction of the HIF target gene CA9 on protein level in HCT116luc cells is inhibited by BAY 87-2243 with an IC50 value of ~2 nM. BAY 87-2243 inhibits mitochondrial oxygen consumption measured by using the oxygen sensitive fluorescence dye LUX-MitoXpress with an IC50 value of ~10 nM. BAY-87-2243 inhibits nuclear HIF-1α protein expression. Administration of BAY-87-2243 for about 18 days significantly reduces HIF-1α protein expression as well as pimonidazole hypoxic fraction (pHF) (mean 2.4% (BAY-87-2243) vs. 17.6% (carrier), p<0.0001), and necrotic fraction (NF) (mean 9% vs. 35.6%, p=0.0002), whereas relative vascular area (RVA) and perfused vessels (PF) remained unchanged.

Nude mice are inoculated with H460 cells subcutaneously and after tumors have been established, animals are treated with BAY 87-2243 (0.5, 1, 2, and 4 mg/kg) for 3 weeks by daily oral gavage. BAY 87-2243 reduced tumor weight dose dependently in line with a dose-dependent reduction of the mRNA expression levels of the HIF-1 target genes CA9, ANGPTL4, and EGLN3, whereas the mRNA expression levels of hypoxia-insensitive EGLN2 gene and of HIF-1α itself are not affected by compound treatment in vivo.

BAY 872243 | BAY872243 | BAY-872243

Angiogenesis

HIF/HIF Prolyl-hydroxylase

HIF-1α

Cancer

——

1227158-85-1

525.53

C26H26F3N7O2

>98% (HPLC)

Ethanol: 8 mg/mL warmed (15.22 mM)

FC(F)(F)OC1=CC=C(C2=NOC(C3=NN(CC4=CC(N5CCN(C6CC6)CC5)=NC=C4)C(C)=C3)=N2)C=C1

1-cyclopropyl-4-[4-[[5-methyl-3-[3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]-1H-pyrazol-1-yl]methyl]-2-pyridinyl]-piperazine

(-20℃)

With Ice Pack

≥ 2 years