[CAS NO. 891494-63-6] SCH900776
PRODUCTS SPECIFICATIONS [891494-63-6]
DESCRIPTION [891494-63-6]
Overview
| MDL | MFCD20922873 |
|---|---|
| Molecular Weight | 376.25 |
| Molecular Formula | C15H18BrN7 |
| SMILES | NC1=C(Br)C([C@H]2CNCCC2)=NC3=C(C4=CN(C)N=C4)C=NN13 |
7 Publications Citing Use of MCE
- [1]Sci Transl Med. 2021 Jan 20;13(577):eaba7401.
- [2]Sci Transl Med. 2018 Jul 18;10(450):eaaq1093.
- [3]Sci Adv. 2022 Jan 21;8(3):eabj8357.
- [4]Cell Syst. 2018 Apr 25;6(4):424-443.e7.
- [5]Blood Cancer J. 2021 Jul 31;11(7):137.
- [6]Mol Cancer Ther. 2018 Dec;17(12):2676-2688.
- [7]Cancer Biol Ther. 2022 Jan 9;1-14.
Summary
IC50 & Target
|
Chk1 3 nM (IC 50 ) |
Chk2 1500 nM (IC 50 ) |
CDK2 160 nM (IC 50 ) |
In Vitro
SCH900776 (300 nM) shows potent inhibitory activities against phosphorylation at ser296-Chk1. SCH900776 (1 μM) causes a 30-fold decrease in the IC 50 for NSC-32065 in MDA-MB-231 cells [1] . The K d value of SCH 900776 for the CHK1 kinase domain is 2 nM. SCH 900776 exhibits an approximate EC 50 of 60 nM in cells exposure to NSC-32065. SCH 900776 induces dose-dependent suppression of CHK1 pS296 and concomitant accumulation of phospho-RPA signal in U2OS cells [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 LY 188011 results in improvements in TTP 10× in the A2780 xenograft systems [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00779584 | Merck Sharp & Dohme LLC |
Hodgkin Disease|Lymphoma, Non-Hodgkin|Neoplasms
|
October 17, 2008 | Phase 1 |
| NCT00907517 | Merck Sharp & Dohme LLC |
Myelogenous Leukemia, Acute|Leukemia, Lymphocytic, Acute|Leukemia, Lymphoblastic, Acute, Philadelphia-Positive|Myelogenous Leukemia, Chronic, Aggressive Phase
|
July 29, 2009 | Phase 1 |
| NCT01870596 | National Cancer Institute (NCI) |
Adult Acute Megakaryoblastic Leukemia|Adult Acute Monoblastic Leukemia|Adult Acute Monocytic Leukemia|Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11|Adult Acute Myeloid Leukemia With Maturation|Adult Acute Myeloid Leukemia With Minimal Differentiation|Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1|Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL|Adult Acute Myeloid Leukemia Without Maturation|Adult Acute Myelomonocytic Leukemia|Adult Erythroleukemia|Adult Pure Erythroid Leukemia|Alkylating Agent-Related Acute Myeloid Leukemia|Recurrent Adult Acute Myeloid Leukemia
|
May 2013 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 265.78 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent 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 |
References
- [1] Montano R, et al. Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites. Mol Cancer Ther. 2012 Feb;11(2):427-38.
- [2] Guzi TJ, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.