Details
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
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4630 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21321066 |
3.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1010 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
20 mg/m² single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
6220 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1220 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4970 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
80 mg/m² single, intravenous dose: 80 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4680 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
200 mg single, intravenous dose: 200 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1420 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
20 mg/m² single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
19000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2250 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5060 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
80 mg/m² single, intravenous dose: 80 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8410 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
200 mg single, intravenous dose: 200 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
20 mg/m² single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7.38 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
80 mg/m² single, intravenous dose: 80 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
6.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
200 mg single, intravenous dose: 200 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
51% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25605849/ |
40 mg/m² single, intravenous dose: 40 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
MK-8776 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
112 mg/m2 single, intravenous (unknown) Highest studied dose Dose: 112 mg/m2 Route: intravenous Route: single Dose: 112 mg/m2 Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 8 Sources: |
|
150 mg/m2 single, intravenous (unknown) Highest studied dose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: |
unhealthy n = 3 Health Status: unhealthy Condition: Advanced Solid Tumors Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. | 2011 Apr |
|
Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites. | 2012 Feb |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01870596
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22869869
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).
Name | Type | Language | ||
---|---|---|---|---|
|
Systematic Name | English | ||
|
Systematic Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
99Y1V29WVE
Created by
admin on Sat Dec 16 01:34:36 GMT 2023 , Edited by admin on Sat Dec 16 01:34:36 GMT 2023
|
PRIMARY | |||
|
DTXSID60237552
Created by
admin on Sat Dec 16 01:34:36 GMT 2023 , Edited by admin on Sat Dec 16 01:34:36 GMT 2023
|
PRIMARY | |||
|
891494-64-7
Created by
admin on Sat Dec 16 01:34:36 GMT 2023 , Edited by admin on Sat Dec 16 01:34:36 GMT 2023
|
PRIMARY | |||
|
46239014
Created by
admin on Sat Dec 16 01:34:36 GMT 2023 , Edited by admin on Sat Dec 16 01:34:36 GMT 2023
|
PRIMARY |