WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205901
CAS#: 1227158-85-1
Description: BAY 87-2243 is a highly potent and selective inhibitor of hypoxia-induced gene activation, which has antitumor activities by inhibition of mitochondrial complex I. BAY 87-2243 mproves local tumor control after fractionated irradiation in a schedule-dependent manner in head and neck human xenografts. BAY-87-2243 markedly decreased nuclear HIF-1α expression and pimonidazole hypoxic fraction already after 3 days of drug treatment. BAY-87-2243 prior to RT significantly reduced TCD50 from 123 to 100 Gy (p=0.037). Additional BAY-87-2243 application during RT did not decrease TCD50.
MedKoo Cat#: 205901
Name: BAY 87-2243
CAS#: 1227158-85-1
Chemical Formula: C26H26F3N7O2
Exact Mass: 525.21
Molecular Weight: 525.54
Elemental Analysis: C, 59.42; H, 4.99; F, 10.85; N, 18.66; O, 6.09
Synonym: BAY 872243; BAY872243; BAY-872243; BAY 87-2243; BAY87-2243; BAY-87-2243;
IUPAC/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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | BAY 87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor. |
| In vitro activity: | To evaluate dose dependency of BAY 87-2243 on HIF-1 transcriptional activity, H460 cells were cultured under normoxia and hypoxia (16 h, 1% pO2) with various concentrations of BAY 87-2243 ranging from 1 to 1000 nmol/L, and the mRNA level of the HIF-1 target genes CA9, adrenomedullin (ADM), and angiopoietin-like protein-4 (ANGPTL4) was quantified by real-time PCR. EGLN2, a PHD known to be expressed independent of the oxygen supply served as a negative control. BAY 87-2243 suppressed HIF-1 target gene expression dose dependently under hypoxia, but a weak reduction of baseline HIF-1 target gene mRNA expression levels was also observed under normoxia. Notably, expression of EGLN2 was not affected by BAY 87-2243 treatment neither under normoxia nor under hypoxia (Fig. 2A). Additional negative controls (genes not regulated by hypoxia) were evaluated by real-time PCR after incubation of normoxic and hypoxic H460 cells with BAY 87-2243 at concentrations up to 10 μmol/L. No signs of unspecific transcription inhibition were observed even at such high dosages (Fig. S1). Reference: Cancer Med. 2013 Oct;2(5):611-24. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24403227/ |
| In vivo activity: | To test the inhibitory effect of BAY-87-2243 on HIF-1α protein expression, tumors were treated with the drug for 3, 5 or 7 consecutive days. Nuclear HIF-1α protein levels were strongly suppressed after 3 days of drug treatment (Figure 1). Cytoplasmic cell extracts showed none or very weak HIF-1α protein expression (data not shown). To study the kinetics of changes in tumor microenvironment induced by BAY-87-2243, hypoxia, vasculature and perfused vessels were examined in tumors after 3, 5 and 7 days of drug treatment. Three daily applications of BAY-87-2243 markedly reduced pHF to 1% as compared with 25% in carrier-treated tumors (p < 0.0001, Figures 2 and and3a).3a). This decrease in pHF remained after BAY-87-2243 treatment for 5 and 7 days. A statistically significant reduction in RVA was found 5 and 7 days after BAY-87-2243 treatment as compared with carrier-treated tumors (p=0.033 and p=0.026, respectively, Figure 3a). BAY-87-2243 did not affect PF at any time point. Necrotic fraction was statistically significantly lower only after 3 days of drug treatment (p=0.018). Reference: Radiat Oncol. 2014 Sep 19;9:207. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25234922/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 25.0 | 47.57 |
The following data is based on the product molecular weight 525.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | 1. 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. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med. 2013 Oct;2(5):611-24. doi: 10.1002/cam4.112. Epub 2013 Aug 20. PMID: 24403227; PMCID: PMC3892793. |
| In vivo protocol: | 1. Helbig L, Koi L, Brüchner K, Gurtner K, Hess-Stumpp H, Unterschemmann K, Baumann M, Zips D, Yaromina A. 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. Radiat Oncol. 2014 Sep 19;9:207. doi: 10.1186/1748-717X-9-207. PMID: 25234922; PMCID: PMC4262387. 2. 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. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med. 2013 Oct;2(5):611-24. doi: 10.1002/cam4.112. Epub 2013 Aug 20. PMID: 24403227; PMCID: PMC3892793. |
1: Chang E, Liu H, Unterschemmann K, Ellinghaus P, Liu S, Gekeler V, Cheng Z, Berndorff D, Gambhir SS. 18F-FAZA PET imaging response tracks the reoxygenation of tumors in mice upon treatment with the mitochondrial complex I inhibitor BAY 87-2243. Clin Cancer Res. 2015 Jan 15;21(2):335-46. doi: 10.1158/1078-0432.CCR-14-0217. Epub 2014 Nov 7. PubMed PMID: 25381339; PubMed Central PMCID: PMC4297600.
2: Helbig L, Koi L, Brüchner K, Gurtner K, Hess-Stumpp H, Unterschemmann K, Baumann M, Zips D, Yaromina A. 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. Radiat Oncol. 2014 Sep 19;9:207. doi: 10.1186/1748-717X-9-207. PubMed PMID: 25234922; PubMed Central PMCID: PMC4262387.
3: 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. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med. 2013 Oct;2(5):611-24. doi: 10.1002/cam4.112. Epub 2013 Aug 20. PubMed PMID: 24403227; PubMed Central PMCID: PMC3892793.
