| Stereochemistry | ABSOLUTE |
| Molecular Formula | C15H18BrN7 |
| Molecular Weight | 376.254 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1C=C(C=N1)C2=C3N=C([C@H]4CCCNC4)C(Br)=C(N)N3N=C2
InChI
InChIKey=GMIZZEXBPRLVIV-VIFPVBQESA-N
InChI=1S/C15H18BrN7/c1-22-8-10(6-19-22)11-7-20-23-14(17)12(16)13(21-15(11)23)9-3-2-4-18-5-9/h6-9,18H,2-5,17H2,1H3/t9-/m0/s1
| Molecular Formula | C15H18BrN7 |
| Molecular Weight | 376.254 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
MK-8776 (SCH-900776) is a checkpoint kinase 1 inhibitor which was developed by Merck for the treatment of cancer. The drug was tested in phase II clinical trials on patients suffering from acute myeloid leukemia (in combination with cytarabine) and in phase I on patients suffering from solid tumors or lymphoma (as monotherapy and in combination with gemcitabine).
Originator
Approval Year
Cmax
AUC
T1/2
Doses
Sourcing
PubMed
Patents
Sample Use Guides
Patients receive cytarabine IV continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor MK-8776 IV over 30 minutes on days 2, 3, 11, and 12.
Route of Administration:
Intravenous
U937 cells were treated (a) for 4 h with combination of cytarabine (50 nM) and MK-8776 (100, 200, 300, 500 nM); (b) for 4 h with cytarabine (0, 5, 10 nM) in the absence or presence of 100; (c) for 24 h with diluent (0.2% DSMO), 50 nM cytarabine, 100 or 300 nM to test the effect of MK-8776 on cytarabine-induced replication checkpoint activation. HL-60 cells were treated (a) for 24 h with diluent (0.2% DMSO), 300 nM cytarabine, 300 nM MK-8776 or 300 nM cytarabine + 300 nM MK-8776; (b) for 24 h with cytarabine (0, 100, 300 nM) in the presence of MK-8776 at 100, 300 or 1000 nM to test how MK-8776 enhances cytarabine-induced apoptosis in human AML cell lines. In the same experiment, ML-1 cells were also treated for 24 h with cytarabine (50-250 nM) and MK-8776 (0, 25, 50, 100 nM).