BAY 87-2243

• CAT Number: I000875
• CAS Number: 1227158-85-1
• Molecular Formula: C26H26F3N7O2
• Molecular Weight: 525.536
• Purity: ≥95%
• Target: HIF
• Solubility: 10 mM in DMSO
• Storage: Store at -20C
• IC50: 2.0 nM(CA9 in HCT116luc cells) [1]
• IUPAC Name: 5-[1-[[2-(4-cyclopropylpiperazin-1-yl)pyridin-4-yl]methyl]-5-methylpyrazol-3-yl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole
• InChI: 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
• InChIKey: CDJNNOJINJAXPV-UHFFFAOYSA-N
• SMILES: CC1=CC(=NN1CC2=CC(=NC=C2)N3CCN(CC3)C4CC4)C5=NC(=NO5)C6=CC=C(C=C6)OC(F)(F)F

BAY 87-2243 is a highly potent and selective inhibitor of hypoxia-induced HIF-1 activation.IC50 Value: 2.0 nM(CA9 in HCT116luc cells) [1]Target: HIF-1in vitro: BAY 87-2243 inhibited luciferase activity with a calculated IC50 value of ~0.7 nmol/L. Hypoxic induction of the HIF target gene CA9 on protein level in HCT116luc cells was inhibited by BAY 87-2243 with an IC50 value of ~2.0 nmol/L. BAY 87-2243 has no effect on PHD-2 activity. BAY 87-2243 activity depends on intact VHL protein and PHD activity. Lead structure BAY 87-2243 was found to inhibit HIF-1α and HIF-2α protein accumulation under hypoxic conditions in non-small cell lung cancer (NSCLC) cell line H460 but had no effect on HIF-1α protein levels induced by the hypoxia mimetics desferrioxamine or cobalt chloride [1]. The combination treatment of BAY 87-2243 with regorafenib resulted in slight regression of tumor growth that was maintained for up to 18 days in A549. Combination of BAY 87-2243 and regorafenib resulted in an additive improvement of the tumor growth inhibition as compared to either agents alone in PC-3 [2].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 [1].

Reference

1:Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth. Schöckel L, Glasauer A, Basit F, Bitschar K, Truong H, Erdmann G, Algire C, Hägebarth A, Willems PH, Kopitz C, Koopman WJ, Héroult M.Cancer Metab. 2015 Oct 20;3:11. doi: 10.1186/s40170-015-0138-0. eCollection 2015. PMID: 26500770 Free PMC Article2:18F-FAZA PET imaging response tracks the reoxygenation of tumors in mice upon treatment with the mitochondrial complex I inhibitor BAY 87-2243. Chang E, Liu H, Unterschemmann K, Ellinghaus P, Liu S, Gekeler V, Cheng Z, Berndorff D, Gambhir SS.Clin Cancer Res. 2015 Jan 15;21(2):335-46. doi: 10.1158/1078-0432.CCR-14-0217. Epub 2014 Nov 7. PMID: 25381339 Free PMC Article3:BAY 87-2243, a novel inhibitor of hypoxia-induced gene activation, improves local tumor control after fractionated irradiation in a schedule-dependent manner in head and neck human xenografts. Helbig L, Koi L, Brüchner K, Gurtner K, Hess-Stumpp H, Unterschemmann K, Baumann M, Zips D, Yaromina A.Radiat Oncol. 2014 Sep 19;9:207. doi: 10.1186/1748-717X-9-207. PMID: 25234922 Free PMC Article4:BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Ellinghaus P, Heisler I, Unterschemmann K, Haerter M, Beck H, Greschat S, Ehrmann A, Summer H, Flamme I, Oehme F, Thierauch K, Michels M, Hess-Stumpp H, Ziegelbauer K.Cancer Med. 2013 Oct;2(5):611-24. doi: 10.1002/cam4.112. Epub 2013 Aug 20. PMID: 24403227 Free PMC Article