WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205901
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.
Hodoodo Cat#: H205901
Name: BAY 87-2243
CAS#: 1227158-85-1
Chemical Formula: C26H26F3N7O2
Exact Mass: 525.21
Molecular Weight: 525.540
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
More Info:
| 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 |
| Formulation protocol: | |
| 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: Kurelac I, Cavina B, Sollazzo M, Miglietta S, Fornasa A, De Luise M, Iorio M, Lama E, Traversa D, Nasiri HR, Ghelli A, Musiani F, Porcelli AM, Iommarini L, Gasparre G. NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors. Open Biol. 2022 Nov;12(11):220198. doi: 10.1098/rsob.220198. Epub 2022 Nov 9. PMID: 36349549; PMCID: PMC9653258.
2: Philip M, Karakka Kal AK, Mathew B, Subhahar MB, Karatt TK, Perwad Z. Metabolic study of hypoxia-inducible factor stabilizers BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes for doping control. Drug Test Anal. 2022 Oct;14(10):1703-1723. doi: 10.1002/dta.3348. Epub 2022 Jul 26. PMID: 35853151.
3: Domingo-Vidal M, Whitaker-Menezes D, Mollaee M, Lin Z, Tuluc M, Philp N, Johnson JM, Zhan T, Curry J, Martinez-Outschoorn U. Monocarboxylate Transporter 4 in Cancer-Associated Fibroblasts Is a Driver of Aggressiveness in Aerodigestive Tract Cancers. Front Oncol. 2022 Jun 22;12:906494. doi: 10.3389/fonc.2022.906494. PMID: 35814364; PMCID: PMC9259095.
4: Lei X, Teng W, Fan Y, Zhu Y, Yao L, Li Y, Zhu S. The protective effects of HIF-1α activation on sepsis induced intestinal mucosal barrier injury in rats model of sepsis. PLoS One. 2022 May 16;17(5):e0268445. doi: 10.1371/journal.pone.0268445. PMID: 35576220; PMCID: PMC9109928.
5: Du J, Wang C, Chen Y, Zhong L, Liu X, Xue L, Zhang Y, Li Y, Li X, Tang C, Su Z, Zhang C. Targeted downregulation of HIF-1α for restraining circulating tumor microemboli mediated metastasis. J Control Release. 2022 Mar;343:457-468. doi: 10.1016/j.jconrel.2022.01.051. Epub 2022 Feb 3. PMID: 35124127.
6: Kimura T, Sakai M, Gojo N, Watanabe M, Uzawa N, Sakai T. The HIF-1α pathway plays a critical role in salivary gland development in ex vivo organ cultures. FEBS Open Bio. 2022 Feb;12(2):460-469. doi: 10.1002/2211-5463.13351. Epub 2021 Dec 24. PMID: 34904400; PMCID: PMC8804608.
7: Wang P, Zhu P, Liu R, Meng Q, Li S. Baicalin promotes extracellular matrix synthesis in chondrocytes via the activation of hypoxia-inducible factor-1α. Exp Ther Med. 2020 Dec;20(6):226. doi: 10.3892/etm.2020.9356. Epub 2020 Oct 15. PMID: 33193840; PMCID: PMC7646699.
8: Zhao L, Wang J, Zhang Y, Wang L, Yu M, Wang F. Vitamin C decreases VEGF expression levels via hypoxia‑inducible factor‑1α dependent and independent pathways in lens epithelial cells. Mol Med Rep. 2020 Jul;22(1):436-444. doi: 10.3892/mmr.2020.11103. Epub 2020 Apr 30. PMID: 32377733; PMCID: PMC7248485.
9: Sica V, Bravo-San Pedro JM, Kroemer G. A strategy for poisoning cancer cell metabolism: Inhibition of oxidative phosphorylation coupled to anaplerotic saturation. Int Rev Cell Mol Biol. 2019;347:27-37. doi: 10.1016/bs.ircmb.2019.07.002. Epub 2019 Jul 29. PMID: 31451215.
10: Zhang Y, Zhang C, Zhao Q, Wei W, Dong Z, Shao L, Li J, Wu W, Zhang H, Huang H, Liu F, Jin S. The miR-873/NDFIP1 axis promotes hepatocellular carcinoma growth and metastasis through the AKT/mTOR-mediated Warburg effect. Am J Cancer Res. 2019 May 1;9(5):927-944. PMID: 31218102; PMCID: PMC6556606.
11: Li YL, Rao MJ, Zhang NY, Wu LW, Lin NM, Zhang C. BAY 87-2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3β activation. Exp Ther Med. 2019 Jun;17(6):4547-4553. doi: 10.3892/etm.2019.7500. Epub 2019 Apr 18. PMID: 31186678; PMCID: PMC6507497.
12: Sica V, Bravo-San Pedro JM, Izzo V, Pol J, Pierredon S, Enot D, Durand S, Bossut N, Chery A, Souquere S, Pierron G, Vartholomaiou E, Zamzami N, Soussi T, Sauvat A, Mondragón L, Kepp O, Galluzzi L, Martinou JC, Hess-Stumpp H, Ziegelbauer K, Kroemer G, Maiuri MC. Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate. Cell Rep. 2019 Apr 16;27(3):820-834.e9. doi: 10.1016/j.celrep.2019.03.058. PMID: 30995479.
13: Basit F, van Oppen LM, Schöckel L, Bossenbroek HM, van Emst-de Vries SE, Hermeling JC, Grefte S, Kopitz C, Heroult M, Hgm Willems P, Koopman WJ. Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell Death Dis. 2017 Mar 30;8(3):e2716. doi: 10.1038/cddis.2017.133. PMID: 28358377; PMCID: PMC5386536.
14: Görtz GE, Horstmann M, Aniol B, Reyes BD, Fandrey J, Eckstein A, Berchner- Pfannschmidt U. Hypoxia-Dependent HIF-1 Activation Impacts on Tissue Remodeling in Graves' Ophthalmopathy-Implications for Smoking. J Clin Endocrinol Metab. 2016 Dec;101(12):4834-4842. doi: 10.1210/jc.2016-1279. Epub 2016 Sep 9. PMID: 27610652.
15: Dilly AK, Lee YJ, Zeh HJ, Guo ZS, Bartlett DL, Choudry HA. Targeting hypoxia-mediated mucin 2 production as a therapeutic strategy for mucinous tumors. Transl Res. 2016 Mar;169:19-30.e1. doi: 10.1016/j.trsl.2015.10.006. Epub 2015 Oct 31. PMID: 26589109.
16: Schöckel L, Glasauer A, Basit F, Bitschar K, Truong H, Erdmann G, Algire C, Hägebarth A, Willems PH, Kopitz C, Koopman WJ, Héroult M. Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth. Cancer Metab. 2015 Oct 20;3:11. doi: 10.1186/s40170-015-0138-0. PMID: 26500770; PMCID: PMC4615872.
17: Dittmann K, Mayer C, Paasch A, Huber S, Fehrenbacher B, Schaller M, Rodemann HP. Nuclear EGFR renders cells radio-resistant by binding mRNA species and triggering a metabolic switch to increase lactate production. Radiother Oncol. 2015 Sep;116(3):431-7. doi: 10.1016/j.radonc.2015.08.016. Epub 2015 Aug 27. PMID: 26320552.
18: 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. PMID: 25381339; PMCID: PMC4297600.
19: 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.
20: 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.
