MK-8776 (SCH-900776)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
SCH-900776是细胞周期检查点激酶1(Chk1)、Chk2和Cdk3的高效选择性抑制剂,其IC50值分别为3 nM、1.5 M和0.16 M。
Chk是一种丝氨酸/苏氨酸激酶,能够感知DNA损伤信号并暂停DNA复制,其也在DNA抗代谢物暴露期间维持复制叉的活力中起重要作用。
体外实验:SCH-900776以剂量依赖的方式抑制Chk1 pS296自磷酸化的积累。SCH-900776处理增殖中的WS1细胞发现Chk1 pS345迅速的剂量依赖性积累,表明正常细胞的循环群诱导Chk1 pS345以应答SCH-900776的抑制,作为无效循环的一部分 [1]。
体内试验:相较于gemcitabine或SCH-900776单独给药,gemcitabine处理BALB/c小鼠后按8 mg/kg的剂量给予SCH-900776能显著诱导增强的肿瘤药效和消退反应[1]。
参考文献:
1. Guzi TJ, Paruch K, Dwyer MP, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Molecular cancer therapeutics. 2011;10(4):591-602.
- 1. Molkentine JM, Molkentine DP, et al. "Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints." Int J Radiat Biol. 2020;1–8. PMID:32073931
- 2. N. Sanjib Banerjee, Dianne Moore, et al. "Targeting DNA Damage Response as a Strategy to Treat HPV Infections." Int. J. Mol. Sci. 2019, 20(21), 5455.
- 3. Bourgeois A, Bonnet S, et al. "Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension." Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1667-1681. PMID:31092016
Storage | Store at -20°C |
M.Wt | 376.25 |
Cas No. | 891494-63-6 |
Formula | C15H18BrN7 |
Solubility | insoluble in H2O; insoluble in EtOH; ≥18.8 mg/mL in DMSO |
Chemical Name | (R)-6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine |
SDF | Download SDF |
Canonical SMILES | BrC(C([C@@H]1CCCNC1)=N2)=C(N)N3C2=C(C4=CN(C)N=C4)C=N3 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1]: | |
细胞系 |
U2OS细胞 |
溶解方法 |
该化合物在DMSO中的溶解度大于18.8 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
2h |
应用 |
在U2OS细胞中,在羟基脲暴露24小时后,SCH 900776以剂量依赖性方式损伤DNA复制能力。从羟基脲封闭释放后,SCH 900776增加细胞凋亡至少48小时。 |
动物实验 [1]: | |
动物模型 |
A2780异种移植的BALB/c小鼠 |
给药剂量 |
4-32 mg/kg |
应用 |
SCH-900776(8 mg/kg)增强肿瘤药效学和回归反应。SCH 900776(16和32 mg/kg)诱导肿瘤反应的增加。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1] Guzi T J, Paruch K, Dwyer M P, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening[J]. Molecular cancer therapeutics, 2011, 10(4): 591-602. |
Description | SCH-900776是Chk1的选择性抑制剂,其IC50值为3 nM。 | |||||
靶点 | Chk1 | CDK2 | Chk2 | |||
IC50 | 3 nM | 0.16 μM | 1.5 μM |
质量控制和MSDS
- 批次: