BI-847325

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H28N4O2
Molecular Weight	464.5582
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC(=O)C#CC1=CC2=C(C=C1)\C(C(=O)N2)=C(\NC3=CC=C(CN(C)C)C=C3)C4=CC=CC=C4

InChI

InChIKey=FLBNLJLONKAPLR-DQSJHHFOSA-N

InChI=1S/C29H28N4O2/c1-4-30-26(34)17-13-20-12-16-24-25(18-20)32-29(35)27(24)28(22-8-6-5-7-9-22)31-23-14-10-21(11-15-23)19-33(2)3/h5-12,14-16,18,31H,4,19H2,1-3H3,(H,30,34)(H,32,35)/b28-27-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27496137 | https://www.ncbi.nlm.nih.gov/pubmed/25873592
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800034007

BI-847325 is a novel, ATP-competitive, orally available inhibitor of Aurora kinases and MEK. In in vitro studies, BI-847325 inhibited the activity of Xenopus laevis Aurora Kinase B with an IC50 of 3 nM; with IC50 values for human Aurora kinase A and Aurora kinase C being 25 and 15 nM, respectively. BI-847325 also inhibited human MEK1 and MEK2 with respective IC50 values of 25 and 4 nM. BI-847325 had been in phase I clinical trials by Boehringer Ingelheim for the treatment of solid tumours. However, there is no development reported for this study.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25873592	Inhibitor 8297	25.0 nM [IC50]
Serine/threonine-protein kinase Aurora-C 10 Target ID: CHEMBL3935 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25873592	Inhibitor 8297	15.0 nM [IC50]
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25873592	Inhibitor 8297	25.0 nM [IC50]
Dual specificity mitogen-activated protein kinase kinase 2 9 Target ID: CHEMBL2964 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25873592	Inhibitor 8297	4.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT01324830 http://adisinsight.springer.com/drugs/800034007	Primary		Approved 8429	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
The Novel ATP-Competitive MEK/Aurora Kinase Inhibitor BI-847325 Overcomes Acquired BRAF Inhibitor Resistance through Suppression of Mcl-1 and MEK Expression.	2015 Jun	25873592
Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases.	2016 Oct	27496137

Patents

Sample Use Guides

In Vivo Use Guide

Mice: In mice bearing 1205Lu and 1205LuR xenografts, BI-847325 (75 mg/kg, p.o.) causes significant tumor suppression without significant alteration in the body weights.

Route of Administration: Oral

In Vitro Use Guide

BI-847325 inhibited BRAF-mutant and vemurafenib-resistant melanoma cells with IC50 ranging from 0.3 nM to 2 uM, and prevents colony formation in six BRAF-mutant melanoma cell lines. Treatment of the cell line panel with BI-847325 (30–300 nM, 28 days) prevented colony formation in 6 BRAF-mutant melanoma cell lines. The growth inhibitory effect of BI-847325 (48h, 1 uM) was also associated with apoptosis induction, with significant levels of cell death being seen at concentrations >100 nM

Name

Type

Language

BI-847325

Code

English

BI847325

Code

English

3-(3-(((4-((DIMETHYLAMINO)METHYL)PHENYL)AMINO)PHENYLMETHYLENE)-2,3-DIHYDRO-2-OXO-1H-INDOL-6-YL)-N-ETHYL-2-PROPYNAMIDE

Systematic Name

English

3-((3Z)-3-(((4-((DIMETHYLAMINO)METHYL)PHENYL)AMINO)(PHENYL)METHYLENE)-2-OXO-2,3-DIHYDRO-1H-INDOL-6-YL)-N-ETHYL-2-PROPYNAMIDE

Systematic Name

English

2-PROPYNAMIDE, 3-(3-(((4-((DIMETHYLAMINO)METHYL)PHENYL)AMINO)PHENYLMETHYLENE)-2,3-DIHYDRO-2-OXO-1H-INDOL-6-YL)-N-ETHYL-

Systematic Name

English

3-((3Z)-3-((4-(DIMETHYLAMINOMETHYL)ANILINO)-PHENYL-METHYLENE)-2-OXO-INDOLIN-6-YL)-N-ETHYL-PROP-2-YNAMIDE

Systematic Name

English

2-PROPYNAMIDE, 3-((3Z)-3-(((4-((DIMETHYLAMINO)METHYL)PHENYL)AMINO)PHENYLMETHYLENE)-2,3-DIHYDRO-2-OXO-1H-INDOL-6-YL)-N-ETHYL-

Systematic Name

English

Code System Code Type Description

MANUFACTURER PRODUCT INFORMATION

BI-847325