1227158-85-1

Basic information

• Product Name: BAY 87-2243
• Synonyms: BAY 87-2243;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;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
• CAS NO: 1227158-85-1
• Molecular Formula: C₂₆H₂₆F₃N₇O₂
• Molecular Weight: 525.53
• Product Categories: Inhibitors
• Mol File: 1227158-85-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 677.7±65.0 °C(Predicted)
• Appearance: /
• 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).
• PKA: 8.43±0.27(Predicted)
• 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.
• CAS DataBase Reference: BAY 87-2243(CAS DataBase Reference)
• NIST Chemistry Reference: BAY 87-2243(1227158-85-1)
• EPA Substance Registry System: BAY 87-2243(1227158-85-1)

Safety Data

• Hazardous Substances Data: 1227158-85-1(Hazardous Substances Data)

Usage

Description

BAY 87-2243 is a potent and selective inhibitor of hypoxia-induced gene activation, specifically targeting HIF-1α and HIF-2α protein accumulation under hypoxic conditions. It also inhibits mitochondrial complex I activity, making it a potential candidate for antitumor treatment, particularly in overcoming chemoand radiotherapy-resistance of hypoxic tumors.

Uses

Used in Anticancer Applications:
BAY 87-2243 is used as an antitumor agent for inhibiting HIF-1α and HIF-2α protein accumulation in non-small cell lung cancer cell line H460. It demonstrates its efficacy by reducing tumor weight in nude mice inoculated with H460 cells and by targeting mitochondrial complex I, which leads to reduced melanoma tumor growth.
Used in Overcoming Therapy Resistance:
BAY 87-2243 is used as a treatment to overcome chemoand radiotherapy-resistance of hypoxic tumors by inhibiting mitochondrial complex I activity. This inhibition affects the HIF-1 effects, making the drug a promising candidate for enhancing the sensitivity and efficacy of conventional cancer treatments.

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.

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

Upstream product

• 27374-25-0 [(1-Ethoxycyclopropyl)oxy]trimethylsilane 
• 1227158-84-0 1-{4-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1H-pyrazol-1-yl)-methyl]pyridin-2-yl}piperazine 
• 1225380-68-6 2-Chloro-4-[(5-methyl-3-{3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl}-1H-pyrazol-1-yl)-methyl]pyridine 

Downstream Products

• 1227158-86-2 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 hydrochloride 
• 1227158-88-4 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 4-sulfamoylbenzoate 

Relevant articles and documents

HETEROCYCLICALLY SUBSTITUTED ARYL COMPOUNDS AS HIF INHIBITORS

The present application relates to novel aryl compounds with heterocyclic substituents, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention