| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H21ClFN3O3S |
| Molecular Weight | 461.937 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)[C@@]3(CC1=NC(NC2=NC=CS2)=CC=C1)CC[C@@H](CC3)OC4=CC=CC(Cl)=C4F
InChI
InChIKey=LCVIRAZGMYMNNT-VVONHTQRSA-N
InChI=1S/C22H21ClFN3O3S/c23-16-4-2-5-17(19(16)24)30-15-7-9-22(10-8-15,20(28)29)13-14-3-1-6-18(26-14)27-21-25-11-12-31-21/h1-6,11-12,15H,7-10,13H2,(H,28,29)(H,25,26,27)/t15-,22-
| Molecular Formula | C22H21ClFN3O3S |
| Molecular Weight | 461.937 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
MK-5108 is a small molecule inhibitor of AuroraA kinase with high selectivity versus Aurora-B and C. It was tested in phase I study against advanced or refractory solid tumors both as a monotherapy or in combination with docetaxel, but this study was terminated early due to toxicities at MK-5108 doses below the anticipated PK exposure target.
Originator
Approval Year
Cmax
AUC
T1/2
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Sourcing
PubMed
Patents
Sample Use Guides
In a randomized phase I study of against advanced or refractory solid tumors MK-5108 was administered p.o. BID Q12h on days 1-2 in 14-21 day cycles either alone (200 to 1800 mg) or in combination (100 to 225 mg) with IV docetaxel 60 mg/m(2).
Route of Administration:
Oral
Recombinant His-tagged human Aurora-A protein was expressed in Escherichia coli and was purified with HisTrap HP column (GE Healthcare). The Aurora-A assay reaction was conducted in the presence of 20 μmol/L ATP, 25 μmol/L Tetra-Kemptide [RRR(GLRRASLG)4R-NH2], 1.0 μCi per well [gamma-33P]-ATP, 0.1 ng per well Aurora-A in 50 mmol/L Tris-HCl (pH 7.4), 15 mmol/L Mg(OAc)2, and 0.2 mmol/L EDTA at 30°C for 40 min. To investigate the inhibition mode of MK-5108 for Aurora-A, the IC50 values of MK-5108 were determined in the presence of different concentrations of ATP. Then, the IC50 value was plotted as a function of ATP concentration to analyze the effect of ATP concentration on the IC50 value of MK-5108.
|
|
TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
0.064 NANOMOLAR (average) |
Showing 1 to 1 of 1 entries
