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
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
| Molecular Formula | C26H26F3N7O2 |
| Molecular Weight | 525.5255 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24403227 | https://www.ncbi.nlm.nih.gov/pubmed/25234922Curator's Comment: Description was created based on several sources, including http://en.pharmacodia.com/web/drug/1_2226.html
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24403227 | https://www.ncbi.nlm.nih.gov/pubmed/25234922
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.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 19:05:32 GMT 2023
by
admin
on
Sat Dec 16 19:05:32 GMT 2023
|
| Record UNII |
5XQ7LE6DZG
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
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) | ||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 | |||
|
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 |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
TARGET -> INHIBITOR |
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
ACTIVE MOIETY |
Lead structure BAY 87-2243 was found to inhibit HIF-1.ALPHA. and HIF-2.ALPHA. protein accumulation under hypoxic conditions in non-small cell lung cancer (NSCLC) cell line H460 but had no effect on HIF-1.ALPHA. protein levels induced by the hypoxia mimetics desferrioxamine or cobalt chloride. BAY 87-2243 had no effect on HIF target gene expression levels in RCC4 cells lacking Von Hippel-Lindau (VHL) activity nor did the compound affect the activity of HIF prolyl hydroxylase-2. Antitumor activity of BAY 87-2243, suppression of HIF-1.ALPHA. protein levels, and reduction of HIF-1 target gene expression in vivo were demonstrated in a H460 xenograft model. BAY 87-2243 did not inhibit cell proliferation under standard conditions. However under glucose depletion, a condition favoring mitochondrial ATP generation as energy source, BAY 87-2243 inhibited cell proliferation in the nanomolar range.
|
||
|
ACTIVE MOIETY |
Originator: Bayer HealthCare; Class: Antineoplastic, Small molecule; Mechanism of Action: Hypoxia-inducible factor-1 alpha inhibitor; Highest Development Phase: Phase I for Solid tumours; Most Recent Events: 09 Aug 2012 Bayer terminates its phase I trial for Solid tumours in Germany, United Kingdom & Norway (NCT01297530), 16 Jul 2012 Bayer completes enrolment in its phase I trial for Solid tumours in Germany, United Kingdom & Norway (NCT01297530), 30 Jun 2012 Phase-I clinical trials in Solid tumours in Norway (PO)
|
