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Details

Stereochemistry ACHIRAL
Molecular Formula C26H26F3N7O2
Molecular Weight 525.5255
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BAY-87-2243

SMILES

CC1=CC(=NN1CC2=CC(=NC=C2)N3CCN(CC3)C4CC4)C5=NC(=NO5)C6=CC=C(OC(F)(F)F)C=C6

InChI

InChIKey=CDJNNOJINJAXPV-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_2226.html

BAY-87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor. BAY 87-2243 inhibits HIF-1 reporter gene activity and CA9 protein expression with IC50 of 0.7 nM and 2 nM, respectively. In hypoxic lung cancer H460 cells, BAY-87-2243 suppresses HIF target gene expression, and inhibits HIF-1α protein accumulation. BAY-87-2243 showed dose-dependent in vivo antitumor efficacy in the H460 lung tumor xenograft model accompanied by a suppression of HIF-1a protein and HIF-1 target genes without any signs of toxicity or body weight loss. Further mode-of-action analyses revealed that BAY-87-2243 exerts its effect on the HIF pathway by blocking mitochondrial complex I activity and thereby reducing HIF protein levels under hypoxia. BAY-87-2243 had been in phase I clinical trials by Bayer for the treatment of malignancies. However, this study has been terminated for the drug-related adverse events.

Originator

Curator's Comment: # Bayer HealthCare

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.7 nM [IC50]
0.7 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I.
2013 Oct
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.
2014 Sep 19
Patents

Patents

Sample Use Guides

Mice: In H460 xenograft mouse model, BAY-87-2243 (4 mg/kg p.o.) reduces tumor weight, HIF-1α protein, and HIF-1 target gene expression levels.
Route of Administration: Oral
BAY-87-2243 inhibits HIF-1a and HIF-2a protein accumulation dose dependently (10 - 100 nmol/L) in total cellular extracts from hypoxic H460 cells
Name Type Language
BAY-87-2243
Common Name English
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)-
Systematic Name English
BAY-872243
Code English
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
Systematic Name English
Code System Code Type Description
MANUFACTURER PRODUCT INFORMATION
BAY-87-2243
Created by admin on Sat Dec 16 19:05:32 GMT 2023 , Edited by admin on Sat Dec 16 19:05:32 GMT 2023
PRIMARY 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-1.ALPHA. 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. (last updated: 1/29/2016)
FDA UNII
5XQ7LE6DZG
Created by admin on Sat Dec 16 19:05:32 GMT 2023 , Edited by admin on Sat Dec 16 19:05:32 GMT 2023
PRIMARY
PUBCHEM
67377767
Created by admin on Sat Dec 16 19:05:32 GMT 2023 , Edited by admin on Sat Dec 16 19:05:32 GMT 2023
PRIMARY
SMS_ID
300000042412
Created by admin on Sat Dec 16 19:05:32 GMT 2023 , Edited by admin on Sat Dec 16 19:05:32 GMT 2023
PRIMARY
EPA CompTox
DTXSID901025725
Created by admin on Sat Dec 16 19:05:32 GMT 2023 , Edited by admin on Sat Dec 16 19:05:32 GMT 2023
PRIMARY
CAS
1227158-85-1
Created by admin on Sat Dec 16 19:05:32 GMT 2023 , Edited by admin on Sat Dec 16 19:05:32 GMT 2023
PRIMARY