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MK-8776 (SCH 900776)

Name: MK-8776 (SCH 900776)
Brand: Selleck Chemicals
SKU: S2735
Rating: 5 (77 reviews)

Catalog No.S2735 Purity:99.98%

MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.

MK-8776 (SCH 900776) Chemical Structure

CAS No. 891494-63-6

Purity & Quality Control

Batch: Purity: 99.98%

99.98

MK-8776 (SCH 900776) Related Products

Related Targets	Chk1 Chk2	Click to Expand
Related Products	AZD7762 Rabusertib (LY2603618) CHIR-124 Prexasertib HCl (LY2606368) PF-477736 BML-277 (Chk2 Inhibitor II) Prexasertib (LY2606368) CCT245737 (SRA737) GDC-0575	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	Click to Expand

Signaling Pathway

Chk Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SKOV3	Growth Inhibition Assay	0.3 µM	8 d		sensitizes the cell lines to	23548269
BxPC-3	Growth Inhibition Assay	10-1000 nM	24-48h		enhances the chemosensitization to	23804422
MiaPaCa-2	Growth Inhibition Assay	10-1000 nM	24-48h		enhances the chemosensitization to	23804422
AsPC-1	Growth Inhibition Assay	10-1000 nM	24-48h		enhances the chemosensitization to	23804422
H1299	Growth Inhibition Assay	500 nM	24 h	DMSO	enhances the chemosensitization to PMX	24113549
H1993	Growth Inhibition Assay	500 nM	24 h	DMSO	enhances the chemosensitization to PMX	24113549
H1437	Growth Inhibition Assay	500 nM	24 h	DMSO	enhances the chemosensitization to PMX	24113549
H23	Growth Inhibition Assay	500 nM	24 h	DMSO	enhances the chemosensitization to PMX	24113549
AsPC-1	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
TK10	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
A498	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
U20S	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
SNB19	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
MDA-MB-435	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
U87	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
HCC2998	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
MDA-MB-231	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
MiaPaCa-2	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
MCF10A	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
HCT116	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
IGROV-1	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
SW620	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
HCT115	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
U251	Growth Inhibition Assay	200/2000 nM	24 h		decreases the IC50 of	24359526
OVCAR-8	Growth Inhibition Assay	0.3 µM	8 d		sensitizes the cell lines to	23548269
MV-4-11	Apoptosis Assay	100-700 nM	48 h		induces apoptosis dose dependently	23536721
U937	Apoptosis Assay	100-700 nM	48 h		induces apoptosis dose dependently	23536721
MOLM-13	Apoptosis Assay	100-700 nM	48 h		induces apoptosis dose dependently	23536721
A2058	Cell Viability Assay	37.5-300 nM	72 h	DMSO	reduces the MK-1775 EC50 by 5-fold to an average of 45 nM	23148684
H2009	Cell Viability Assay	500 nM	72 h	DMSO	results in G1/S-phase accumulation combined with MK-1775	23148684
Su.86.86	Cell Viability Assay	500 nM	72 h	DMSO	results in G1/S-phase accumulation combined with MK-1775	23148684
HRE	Cell Viability Assay	500 nM	72 h	DMSO	results in G1/S-phase accumulation combined with MK-1775	23148684
HMEC	Cell Viability Assay	500 nM	72 h	DMSO	results in G1/S-phase accumulation combined with MK-1775	23148684
U2OS	Function Assay	2 µM	0-24 h		induces phosphorylation of Chk1 at serine 345 at both concentrations as early as 2 h after administration	22937147
U2OS	Growth Inhibition Assay	0-10 µM	24/48 h		inhibits cell growth dose dependently	22937147
U937	Function Assay	100-500 nM	4 h		decreases the cytarabine-induced Chk1 autophosphorylation at Ser296 and prevents Cdc25A downregulation	22869869
U937	Function Assay	100 nM	4 h		reverses the cytarabine-induced inhibition of 3H-thymidine incorporation into DNA	22869869
U937	Function Assay	100-500 nM	4 h		induces increased phosphorylation of H2AX	22869869
HL-60	Apoptosis Assay	30/100/300 nM	24 h	DMSO	enhances cytarabine-induced apoptosis	22869869
ML-1	Apoptosis Assay	25/50/100 nM	24 h	DMSO	enhances cytarabine-induced apoptosis	22869869
HCT116	Function Assay	1 µM	24 h		abrogates of cell cycle arrest	22510560
U2OS	Function Assay	1 µM	24 h		abrogates of cell cycle arrest	22510560
Sf9	Function assay				Inhibition of recombinant CDK2/Cyclin A expressed in insect Sf9 cells assessed as inhibition of [33P]-ATP incorporation into biotinylated histone H1 after 1 hr by liquid scintillation counting, IC50 = 0.16 μM.	21094607
Click to View More Cell Line Experimental Data

Biological Activity

Description

MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2.

Targets

Chk1 ^[1] (Cell-free assay)	CDK2 ^[1] (Cell-free assay)
3 nM	0.16 μM

In vitro
In vitro	SCH 900776 is a less potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double stranded DNA breaks. Additionally, SCH 900776 suppresses accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776 is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to SCH 900776 as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK.^[1]
Kinase Assay	Chk1 SPA assay
Kinase Assay	An in vitro assay utilizing recombinant His-Chk1 expressed in the baculovirus expression system as an enzyme source and biotinylated peptide based upon CDC25C as substrate. His-Chk1 is diluted to 32 nM in kinase buffer containing 50 mM Tris pH 8.0, 10 mM MgCl₂, and 1 mM DTT. CDC25C (CDC25 Ser216 C-term biotinylated peptide) peptide is diluted to 1.93 μM in kinase buffer. For each kinase reaction, 20 μL of 32 nM Chk1 enzyme solution and 20 μL of 1.926 μM CDC25C are mixed and combined with 10 μL of SCH 900776 diluted in 10% DMSO, making final reaction concentrations of 6.2 nM Chk1, 385 nM CDC25C and 1% DMSO after addition of start solution. The reaction is started by addition of 50 μL of start solution consisting of 2 μM ATP and 0.2 μCi of ³³P-ATP, making a final reaction concentration of 1 μM ATP, with 0.2 μCi of ³³P-ATP per reaction. Kinase reactions run for 2 hours at room temperature and are stopped by the addition of 100 μL of stop solution consisting of 2 M NaCl, 1% H₃PO₄, and 5 mg/mL Streptavidin-coated SPA beads. SPA beads are captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads are washed twice with 2 M NaCl and twice with 2 M NaCl with 1% phosphoric acid. Signal is then assayed using a TopCount 96-well liquid scintillation counter. Dose-response curves are generated from duplicate 8 point serial dilutions of SCH 900776. IC50 values are derived by nonlinear regression analysis.
Cell Research	Cell lines	mESCs
	Concentrations	10 μM
	Incubation Time	1 h
	Method	Cells were treated with inhibitors or vehicle for 1 hour
Experimental Result Images	Methods	Biomarkers	Images	PMID
Experimental Result Images	Western blot	Cyclin E / pY15-CDK / γH2AX p-chk1(ser345) / CDC25A		26595527

In Vivo
In vivo	Dose escalation of SCH 900776 (16 mg/kg and 32 mg/kg) induces incremental improvements in tumor response. Importantly, doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity on hematological parameters in BALB/c mice. ^[1]
Animal Research	Animal Models	Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells
	Dosages	~50 mg/kg
	Administration	Administered intraperitoneally

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00779584	Completed	Hodgkin Disease\|Lymphoma Non-Hodgkin\|Neoplasms	Merck Sharp & Dohme LLC	October 17 2008	Phase 1

References

[4] Grow EJ, et al. Nat Genet. 2021 Aug;53(8):1207-1220.

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Chemical Information & Solubility

Molecular Weight	376.25	Formula	C₁₅H₁₈BrN₇
CAS No.	891494-63-6	SDF	Download MK-8776 (SCH 900776) SDF
Smiles	CN1C=C(C=N1)C2=C3N=C(C(=C(N3N=C2)N)Br)C4CCCNC4
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 75 mg/mL ( (199.33 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	4%DMSO 1 30%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (13.29mM)	Taking the 1 mL working solution as an example, add 40 μL of 125 mg/ml clarified DMSO stock solution to 300 μL of propylene glycol, mix evenly to clarify it; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
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Frequently Asked Questions

Question 1:
I would like to know whether your product S2735 is the optically pure R enantiomer or whether it is a racemic mix.

Answer:
Our S2735 MK-8776 (SCH 900776) is R enantiomer.

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