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
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-
| Molecular Formula | C29H28N4O2 |
| Molecular Weight | 464.5582 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27496137 | https://www.ncbi.nlm.nih.gov/pubmed/25873592Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800034007
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 | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL4722 |
25.0 nM [IC50] | ||
Target ID: CHEMBL3935 |
15.0 nM [IC50] | ||
Target ID: CHEMBL3587 |
25.0 nM [IC50] | ||
Target ID: CHEMBL2964 |
4.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
| Value | Dose | Co-administered | 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 |
Funbound
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Febrile neutropenia, Vomiting... Dose limiting toxicities: Febrile neutropenia (grade 3, 67%) Sources: Vomiting (grade 3, 33%) Diarrhea (grade 3, 33%) Hypokalemia (33%) |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Febrile neutropenia, Neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 4, 33%) Sources: Neutropenia (grade 4, 33%) |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Vomiting, Diarrhea... Dose limiting toxicities: Vomiting (grade 3, 16.7%) Sources: Diarrhea (grade 3, 16.7%) Decreased appetite (16.7%) |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Febrile neutropenia, Thrombocytopenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 16.7%) Sources: Thrombocytopenia (grade 3, 16.7%) |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Febrile neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 3, 16.7%) Sources: |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Troponin I increase... Dose limiting toxicities: Troponin I increase (grade 3, 16.7%) Sources: |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Fatigue... |
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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| 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: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes | ||||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive Inhibitor of MEK and Aurora Kinases. | 2016-10 |
|
| 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 |
Patents
Sample Use Guides
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
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
| Substance Class |
Chemical
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BI-847325
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PRIMARY | BI-847325: Item NO. 18301, CAS NO. 1207293-36-4BI-847325 is a selective dual MEK/Aurora kinase inhibitor with IC50 values of 3, 25, 15, 25, and 4 nM for X. laevis Aurora B, human Aurora A and Aurora C, and human MEK1 and MEK2, respectively. It can inhibit the growth and survival of both treatment-naive and drug-resistant melanoma cell lines, decreasing the expression of MEK and Mcl-1 while increasing the expression of pro-apoptotic protein Bim.1 At 70 mg/kg, BI-847325 induces apoptosis in treatment-naive and drug-resistant xenografted melanoma in vivo. | ||
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1207293-36-4
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ACTIVE MOIETY |
Originator: Boehringer Ingelheim; Class: Antineoplastic; Mechanism of Action: Aurora kinase A inhibitor, Aurora kinase B inhibitor, Aurora kinase C inhibitor, Mitogen-activated protein kinase inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phase: No development reported for Solid tumours; Most Recent Events: 16 Jul 2016 No recent reports of development identified for phase-I development in Solid-tumours in Belgium (PO), 01 Oct 2013 Boehringer Ingelheim completes a phase I trial in Solid tumours in Belgium (NCT01324830), 31 Mar 2011 Phase-I clinical trials in Solid tumours in Belgium (PO)
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ACTIVE MOIETY |
Results: Sixty-nine patients (Schedule A, n = 47, Schedule B, n = 22) were treated. The MTD was 120 mg per day for Schedule A (cumulative dose of 1680 mg per 3-week cycle) and 150 mg per day for Schedule B (cumulative dose of 2250 mg per 3-week cycle). Reversible hematologic and gastrointestinal toxicities were the most common dose-limiting toxicities. One patient with esophageal cancer (receiving 160 mg BI 847325, Schedule A) experienced a partial response for 67 days, and 21 patients (n = 11 (23.4 %), Schedule A, n = 10 (45.5 %), Schedule B) had stable disease. Pharmacokinetic analyses showed at least bi-exponential disposition, with high inter-subject variability. There was no obvious relationship between markers of MEK or Aurora kinase inhibition and exposure to BI 847325 (exploratory analysis).
Conclusions: This first-in-human trial suggests that BI 847325 has an acceptable safety profile. However, due to insufficient drug exposure at the MTD to achieve relevant MEK inhibition, a decision was taken to halt the development of BI 847325.
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ACTIVE MOIETY |
Official Title: An Open Label Phase Ia/Ib Study of Two Dosing Schedules of BI 847325, Orally Administered Once a Day in Patients With Advanced Solid Tumours, With Repeated Cyclic Administration in Patients With Clinical Benefit
Purpose: The aim of the Phase Ia (dose escalation) part of this trial is to assess the MTD of BI 847325 administered at escalating doses in 2 treatment arms. In the Phase Ib expansion part of the trial, the aim is to further evaluate the safety profile of BI 847325 at the recommended dose and schedule and to assess target modulation and the potential antitumour efficacy in patients with selected tumour types.
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