Molecular Weight (MW)

525.53

Formula

C26H26F3N7O2

CAS No.

1227158-85-1

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: <1 mg/mL

Water: <1 mg/mL

Ethanol: 8 mg/mL (15.22 mM)

Other info

Chemical Name: 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
InChi Key: CDJNNOJINJAXPV-UHFFFAOYSA-N
InChi Code: InChI=1S/C26H26F3N7O2/c1-17-14-22(25-31-24(33-38-25)19-2-6-21(7-3-19)37-26(27,28)29)32-36(17)16-18-8-9-30-23(15-18)35-12-10-34(11-13-35)20-4-5-20/h2-3,6-9,14-15,20H,4-5,10-13,16H2,1H3
SMILES Code: FC(F)(F)OC1=CC=C(C2=NOC(C3=NN(CC4=CC(N5CCN(C6CC6)CC5)=NC=C4)C(C)=C3)=N2)C=C1

Synonyms

BAY-872243; BAY 872243; BAY-872243; BAY-87-2243; BAY87-2243; BAY 87-2243

In Vitro

In vitro activity: BAY 87-2243 inhibits HIF-1 reporter gene activity and CA9 protein expression with IC50 of 0.7 nM and 2 nM, respectively. In hypoxic lung cancer H460 cells, BAY 87-2243 suppresses HIF target gene expression, and inhibits HIF-1α protein accumulation. Under glucose depletion, BAY 87-2243 inhibits cell proliferation via interference with mitochondrial function.

Kinase Assay: BAY 87-2243 inhibits luciferase activity with a calculated IC50 value of ~0.7 nM.

Cell Assay: Cells were plated at 3 × 10E4 cells/well and incubated overnight before BAY 87-2243 (5 mmol/L in DMSO) were added and plates were placed in a hypoxic chamber for 16 h at 1% pO2. Results are given as luminescence counts in arbitrary units after subtraction of baseline levels from normoxic, nontreated controls. For the measurement of cellular complex I activity, H1299 cells were cotransfected with a pcDNA3 vector encoding for Pyrearinus termitilluminans larval click beetle luciferase. Clones (H1299tluc) showing high luminescence and dose-dependent rotenone sensitivity were subcloned and then used for further in depth analysis of cellular complex I activity by luminescence measurements.

In Vivo

Nude mice were inoculated with H460 cells subcutaneously and after tumors have been established, animals were treated with BAY 87-2243 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 were not affected by compound treatment in vivo. H460 cells was inhibited by BAY 87-2243 with an EC50 of ~3 nmol/L, indicating that BAY 87-2243 is an inhibitor of mitochondrial function.

Animal model

Mice bearing lung carcinoma H460 xenografts

Formulation & Dosage

Formulated in 1% (v/v) solution of ethanol/solutol/water (10/40/50%); 4 mg/kg/d; p.o.

References

Cancer Med. 2013 Oct;2(5):611-24.

(A) Chemical structure of BAY 87-2243. (B) BAY 87-2243 suppresses hypoxia-induced reporter gene activity (left), and CA9 protein levels in vitro in HCT-116 cell lysates (right). Cancer Med. 2013 Oct;2(5):611-24.

BAY 87-2243 is inactive in RCC4 cells lacking functional VHL protein or in H460 cells silenced for EGLN1. Cancer Med. 2013 Oct;2(5):611-24.

BAY 87-2243 reduces tumor weight, hypoxia-inducible factor (HIF)-1α protein levels, and HIF-1 target gene expression in H460 xenograft tumors. Cancer Med. 2013 Oct;2(5):611-24.