| Identification | Back Directory | [Name]
BAY 87-2243 | [CAS]
1227158-85-1 | [Synonyms]
CS-1786
BAY 87-2243
BAY 87-2243 USP/EP/BP
BAY 87-2243 BAY87-2243
BAY87 2243;BAY 87 2243;BAY87-2243
5-(1-((2-(4-cyclopropylpiperazin-1-yl)pyridin-4-yl)methyl)-5-methyl-1H-pyrazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole
1-cyclopropyl-4-{4-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1H-pyrazol-1-yl)methyl]pyridin-2-yl}piperazine
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
Piperazine, 1-cyclopropyl-4-[4-[[5-methyl-3-[3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl]-1H-pyrazol-1-yl]methyl]-2-pyridinyl]-
1-cyclopropyl-4-{4-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1H-pyrazol-1-yl)methyl]pyridin-2-yl}piperazine BAY87-2243 | [Molecular Formula]
C26H26F3N7O2 | [MDL Number]
MFCD28143915 | [MOL File]
1227158-85-1.mol | [Molecular Weight]
525.53 |
| Chemical Properties | Back Directory | [Boiling point ]
677.7±65.0 °C(Predicted) | [density ]
1.47±0.1 g/cm3(Predicted) | [storage temp. ]
RT | [solubility ]
Soluble in DMSO (up to 25 mg/ml) or in Ethanol (10 mg/ml). | [form ]
solid | [pka]
8.43±0.27(Predicted) | [color ]
White | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months. |
| Hazard Information | Back Directory | [Description]
BAY 87-2243 (1227158-85-1) potently inhibits HIF-1 reporter gene activity (IC50?= 0.7 nM) and CA9 protein expression (IC50?= 2.0 nM).1?It inhibited HIF-1α and HIF-2α protein accumulation in hypoxic H460 cells and reduced tumor weight in nude mice inoculated with H460 cells. BAY 87-2243 potently inhibits mitochondrial complex I activity (IC50?= 10 nM in mitochondria isolated from PC3 cells) leading to its HIF-1 effects. It has no effect on mitochondrial complex III. BAY 87-2243 reduced melanoma tumor growth?via?its targeting of mitochondrial complex I.2,3 | [Uses]
BAY 87-2243 is a highly potent and selective inhibitor of hypoxia-induced gene activation. It is found to inhibit HIF-1α and HIF-2α protein accumulation under hypoxic conditions in non-small cell lung cancer cell line H460. It inhibits mitochondrial complex I activity and therefore may be used in antitumor treatment to overcome chemo- and radiotherapy- resistance of hypoxic tumors. | [Enzyme inhibitor]
This Hif1a inhibitor (FW = 525.53 g/mol; CAS 1227158-85-1; Solubility:
<1 mg/mL DMSO or H2O) targets the transcription factor hypoxia-inducible
factor-1 (HIF-1), which plays an essential role in tumor development, tumor
progression, and resistance to chemo- and radiotherapy. BAY 87-2243
inhibits HIF-1α and HIF-2α accumulation under hypoxic conditions in the
H460 Non-Small Cell Lung Cancer (NSCLC) cell line but is without effect
on HIF-1α protein levels that are induced by such hypoxia mimetics
asdesferrioxamine or cobalt chloride. BAY 87-2243 has no effect on HIF
target gene expression levels in RCC4 cells lacking Von Hippel-Lindau
(VHL) activity; nor does it affect the activity of HIF prolyl hydroxylase-2.
Antitumor activity of BAY 87-2243, suppression of HIF-1α protein levels,
and reduction of HIF-1 target gene expression in vivo have been
demonstrated in a H460 xenograft model. BAY 87-2243 does not inhibit cell
proliferation under standard conditions. Upon glucose depletion, a condition
favoring mitochondrial ATP generation as energy source, BAY 87-2243
inhibits cell proliferation in the low-nM range. In a mouse model for BRAF-
mutant melanoma, BAY 87-2243-mediated complex I inhibition induces
melanoma cell death in vitro and reduces melanoma tumor growth in various
mouse models in vivo. This effect is mediated through BAY 87-2243-
induced stimulation of mitochondrial ROS production, leading to oxidative
damage and subsequent cell death. BAY 87-2243 displays increased anti-
tumor efficacy compared to single agent treatment, when combined with the
BRAF inhibitor vemurafenib in nude mice with BRAF mutant melanoma
xenografts. | [storage]
Store at -20°C | [References]
1) Ellinghaus?et al.?(2013),?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.,2?611
2) Schockel?et al.?(2015),?Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth; Cancer Metab.,?3?11
3) Basit?et al.?(2017),?Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells; Cell Death Discov.,?8?e2716 |
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