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=CC=C2C(NC(=O)\C2=C(/NC3=CC=C(CN(C)C)C=C3)C4=CC=CC=C4)=C1

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 8504	25.0 nM [IC50]
Serine/threonine-protein kinase Aurora-C 10 Target ID: CHEMBL3935 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25873592	Inhibitor 8504	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 8504	25.0 nM [IC50]
Dual specificity mitogen-activated protein kinase kinase 2 10 Target ID: CHEMBL2964 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25873592	Inhibitor 8504	4.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: https://clinicaltrials.gov/ct2/show/NCT01324830 http://adisinsight.springer.com/drugs/800034007	Primary		Approved 8583	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
2.17 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.34 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	9 mg 1 times / day multiple, oral dose: 9 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.64 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	13 mg 1 times / day multiple, oral dose: 13 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.79 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	19 mg 1 times / day multiple, oral dose: 19 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.89 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	26 mg 1 times / day multiple, oral dose: 26 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.61 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	33 mg 14 times / 2 weeks multiple, oral dose: 33 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.7 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	46 mg 1 times / day multiple, oral dose: 46 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
20.3 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	63 mg 1 times / day multiple, oral dose: 63 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.6 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	86 mg 1 times / day multiple, oral dose: 86 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.5 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	90 mg 1 times / day multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30.4 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	130 mg 1 times / day multiple, oral dose: 130 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
20.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
94.9 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	180 mg 1 times / day multiple, oral dose: 180 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.43 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.17 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	9 mg single, oral dose: 9 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.64 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	13 mg single, oral dose: 13 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.02 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	19 mg single, oral dose: 19 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.12 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	26 mg single, oral dose: 26 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.16 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	33 mg single, oral dose: 33 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.87 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	46 mg single, oral dose: 46 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	63 mg single, oral dose: 63 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25.7 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	86 mg single, oral dose: 86 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.9 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
62.5 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25.7 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	130 mg single, oral dose: 130 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.8 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
147 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	180 mg single, oral dose: 180 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
7.37 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.16 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	9 mg 1 times / day multiple, oral dose: 9 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.6 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	13 mg 1 times / day multiple, oral dose: 13 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.7 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	19 mg 1 times / day multiple, oral dose: 19 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.2 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	26 mg 1 times / day multiple, oral dose: 26 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
39 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	33 mg 14 times / 2 weeks multiple, oral dose: 33 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
165 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	46 mg 1 times / day multiple, oral dose: 46 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
192 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	63 mg 1 times / day multiple, oral dose: 63 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
228 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	86 mg 1 times / day multiple, oral dose: 86 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
146 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
342 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	90 mg 1 times / day multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
385 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	130 mg 1 times / day multiple, oral dose: 130 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
199 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1030 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	180 mg 1 times / day multiple, oral dose: 180 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.86 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	13 mg single, oral dose: 13 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.77 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	19 mg single, oral dose: 19 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.8 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	26 mg single, oral dose: 26 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
36.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	33 mg single, oral dose: 33 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
68.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	46 mg single, oral dose: 46 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
111 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	63 mg single, oral dose: 63 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
170 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	86 mg single, oral dose: 86 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
142 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
551 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
220 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
99.4 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	130 mg single, oral dose: 130 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
79.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1200 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	180 mg single, oral dose: 180 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
16.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	26 mg 1 times / day multiple, oral dose: 26 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	33 mg 14 times / 2 weeks multiple, oral dose: 33 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	46 mg 1 times / day multiple, oral dose: 46 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	63 mg 1 times / day multiple, oral dose: 63 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	86 mg 1 times / day multiple, oral dose: 86 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	90 mg 1 times / day multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	130 mg 1 times / day multiple, oral dose: 130 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	180 mg 1 times / day multiple, oral dose: 180 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	33 mg single, oral dose: 33 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.51 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	46 mg single, oral dose: 46 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	63 mg single, oral dose: 63 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.43 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	86 mg single, oral dose: 86 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.37 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	130 mg single, oral dose: 130 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26650227/	180 mg single, oral dose: 180 mg route of administration: Oral experiment type: SINGLE co-administered:	BI-847325 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27496137/			BI-847325 plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
160 mg 1 times / day multiple, oral Highest studied dose Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Febrile neutropenia, Vomiting... Dose limiting toxicities: Febrile neutropenia (grade 3, 67%) Vomiting (grade 3, 33%) Diarrhea (grade 3, 33%) Hypokalemia (33%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
180 mg 5 times / week multiple, oral Highest studied dose Dose: 180 mg, 5 times / week Route: oral Route: multiple Dose: 180 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Febrile neutropenia, Neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 4, 33%) Neutropenia (grade 4, 33%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Vomiting, Diarrhea... Dose limiting toxicities: Vomiting (grade 3, 16.7%) Diarrhea (grade 3, 16.7%) Decreased appetite (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
150 mg 5 times / week multiple, oral MTD Dose: 150 mg, 5 times / week Route: oral Route: multiple Dose: 150 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Febrile neutropenia, Thrombocytopenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 16.7%) Thrombocytopenia (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
130 mg 5 times / week multiple, oral Studied dose Dose: 130 mg, 5 times / week Route: oral Route: multiple Dose: 130 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Febrile neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
26 mg 1 times / day multiple, oral Studied dose Dose: 26 mg, 1 times / day Route: oral Route: multiple Dose: 26 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Troponin I increase... Dose limiting toxicities: Troponin I increase (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
33 mg 1 times / day multiple, oral Studied dose Dose: 33 mg, 1 times / day Route: oral Route: multiple Dose: 33 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/

AEs

AE	Significance	Dose	Population
Hypokalemia	33% DLT	160 mg 1 times / day multiple, oral Highest studied dose Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Diarrhea	grade 3, 33% DLT	160 mg 1 times / day multiple, oral Highest studied dose Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Vomiting	grade 3, 33% DLT	160 mg 1 times / day multiple, oral Highest studied dose Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Febrile neutropenia	grade 3, 67% DLT	160 mg 1 times / day multiple, oral Highest studied dose Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Febrile neutropenia	grade 4, 33% DLT	180 mg 5 times / week multiple, oral Highest studied dose Dose: 180 mg, 5 times / week Route: oral Route: multiple Dose: 180 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Neutropenia	grade 4, 33% DLT	180 mg 5 times / week multiple, oral Highest studied dose Dose: 180 mg, 5 times / week Route: oral Route: multiple Dose: 180 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Decreased appetite	16.7% DLT	120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Diarrhea	grade 3, 16.7% DLT	120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Vomiting	grade 3, 16.7% DLT	120 mg 1 times / day multiple, oral MTD Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Febrile neutropenia	grade 3, 16.7% DLT	150 mg 5 times / week multiple, oral MTD Dose: 150 mg, 5 times / week Route: oral Route: multiple Dose: 150 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Thrombocytopenia	grade 3, 16.7% DLT	150 mg 5 times / week multiple, oral MTD Dose: 150 mg, 5 times / week Route: oral Route: multiple Dose: 150 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Febrile neutropenia	grade 3, 16.7% DLT	130 mg 5 times / week multiple, oral Studied dose Dose: 130 mg, 5 times / week Route: oral Route: multiple Dose: 130 mg, 5 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Troponin I increase	grade 3, 16.7% DLT	26 mg 1 times / day multiple, oral Studied dose Dose: 26 mg, 1 times / day Route: oral Route: multiple Dose: 26 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/
Fatigue	grade 3, 16.7% DLT	33 mg 1 times / day multiple, oral Studied dose Dose: 33 mg, 1 times / day Route: oral Route: multiple Dose: 33 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP1 232	supressor 160 Sources: https://pubmed.ncbi.nlm.nih.gov/36482411/	yes
P-gp 1932	supressor 160 Sources: https://pubmed.ncbi.nlm.nih.gov/36482411/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/135567102#section=BioAssay-Results Page: 7 \| 81	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/26650227/

PubMed

Title	Date	PubMed
Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases.	2016-10	27496137
The Novel ATP-Competitive MEK/Aurora Kinase Inhibitor BI-847325 Overcomes Acquired BRAF Inhibitor Resistance through Suppression of Mcl-1 and MEK Expression.	2015-06	25873592

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

Preferred Name

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