1. Cell Cycle/DNA Damage
  2. Checkpoint Kinase (Chk)

SCH900776 (Synonyms: MK-8776)

Cat. No.: HY-15532 Purity: 99.65%
Handling Instructions

SCH900776 is a potent, selective and orally bioavailable inhibitor of checkpoint kinase1 (Chk1) with IC50 of 3 nM, and has much greater selectivity than Chk2 (IC50=1500 nM) and cyclin-dependent kinase CDK2 (IC50=160 nM).

For research use only. We do not sell to patients.
SCH900776 Chemical Structure

SCH900776 Chemical Structure

CAS No. : 891494-63-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 145 In-stock
5 mg USD 132 In-stock
10 mg USD 192 In-stock
50 mg USD 540 In-stock
100 mg USD 900 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of SCH900776:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

SCH900776 is a potent, selective and orally bioavailable inhibitor of checkpoint kinase1 (Chk1) with IC50 of 3 nM, and has much greater selectivity than Chk2 (IC50=1500 nM) and cyclin-dependent kinase CDK2 (IC50=160 nM).

IC50 & Target

IC50: 3 nM (Chk1), 160 nM (CDK2), 1500 nM (Chk2)[2]

In Vitro

SCH900776 (300 nM) shows potent inhibitory activities against phosphorylation at ser296-Chk1. SCH900776 (1 μM) causes a 30-fold decrease in the IC50 for hydroxyurea in MDA-MB-231 cells[1]. The Kd value of SCH 900776 for the CHK1 kinase domain is 2 nM. SCH 900776 exhibits an approximate EC50 of 60 nM in cells exposure to hydroxyurea. SCH 900776 induces dose-dependent suppression of CHK1 pS296 and concomitant accumulation of phospho-RPA signal in U2OS cells[2].

In Vivo

SCH 900776 induces the γ-H2AX biomarker at 4 mg/kg (i.p.), and enhances tumor pharmacodynamic and regression responses in A2780 xenograft model. SCH 900776 (16 and 32 mg/kg, i.p.) induces incremental improvements in tumor response. Escalation of SCH 900776 dose to 20 and 50 mg/kg in combination with gemcitabine results in improvements in TTP 10× in the A2780 xenograft systems[2].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.6578 mL 13.2890 mL 26.5781 mL
5 mM 0.5316 mL 2.6578 mL 5.3156 mL
10 mM 0.2658 mL 1.3289 mL 2.6578 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[2]

The Kinase Profiler service is used to generate general selectivity data for SCH 900776 against a broad range of serine/threonine and tyrosine kinases. Assays are typically run at two concentrations of SCH 900776 (0.5 and 5 μM), at a fixed (10 μM) concentration of ATP. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

For cell growth assays, cells are seeded at low density (500-1000 cells) in 96-well plates and then incubated with drug for 24 h (8 wells per concentration). Following treatment, cells are washed and grown in fresh media for 5-7 days at 37°C. Prior to attaining confluence, cells are washed, lysed, and stained with Hoechst 33258. Fluorescence is read on a microplate spectrofluorometer. Results are expressed as mean and standard error for the concentration of drug that inhibited growth by 50%. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

SCH 900776 is formulated in 20% hydroxypropyl β-cyclodextrin.

For tumor implantation, specific cell lines are grown in vitro, washed once with PBS and resuspended in 50% Matrigel in PBS to a final concentration of 4×107 to 5×107 cells per mL. Nude mice are injected with 0.1 mL of this suspension subcutaneously in the flank region. Tumor length (L), width (W), and height (H) are measured by a caliper twice a week on each mouse and then used to calculate tumor volume using the formula: (L×W×H)/2. Animals (N=10) are randomized to treatment groups and treated intraperitoneally with either SCH 900776 (formulated in 20% hydroxypropyl β-cyclodextrin) or individual chemotherapeutic agents, formulated as recommended. Tumor volumes and body weights are measured during and after the treatment periods. Data are recorded as means±SEM before being normalized to starting volume. Time to progression to 10x starting volume (TTP 10x) is monitored in some experiments. For pharmacodynamic marker analyses in mice, tumors and adjacent skin are collected at necropsy, fixed overnight in 10% formalin, and washed/stored in 70% ethanol. For skin punch biopsies, an area of approximately 4 square inches is shaved. Rats are anesthetized using inhaled isofluorane and dogs are locally anesthetized using subcutaneous administration of lidocaine. Samples are collected using a 4 mm biopsy punch. Skin punches are fixed in 10% formalin overnight before washing/storage in 70% ethanol. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

376.25

Formula

C₁₅H₁₈BrN₇

CAS No.

891494-63-6

SMILES

NC1=C(Br)C([[email protected]]2CNCCC2)=NC3=C(C4=CN(C)N=C4)C=NN13

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Product Name:
SCH900776
Cat. No.:
HY-15532
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